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This setting' world is populated by witch covens that function as both royal houses and political entities. They are matriarchial, with witches had the head of families who directly control their houses and have indirect control over smaller branch clans. The concept of marriage works very differently from our world. Instead of marrying individuals, it is the practice of many houses for males marry into an entire clan. In other countries, exogamy is the norm, where individuals are chosen to concieve a child together while remaining in their birth clan. A mother's brother is considered the true fathers of their children, and spend more time raising them than a biological dad.

In our world, the concept of the nuclear household is the most stable form of family. Extramarital affairs and multiple partners are looked down on, and having multiple father's to your children is shameful. However, this world sees things in a different light. Having multiple kids by different men are encouraged because it adds more genes to the pool and builds relationships with other houses in the form of alliances, trade deals, etc.

This is a radical departure from most cultures but is a big part of the setting. How do you make it completely normal and a positive thing when the reader most likely has a different experience?

The reader doesn't have to agree with the setting of your story: he just has to understand it.

I'll basically answer with a longer version of "show, don't tell".
Our society may look down on extramarital affairs and multiple partners, but the reader has to understand that this is not our society.

Since the covens-clans are a big part of your setting, you should give yourself time to describe them, exploring every nook and cranny of their culture before moving on with the actual plot. Better still, show this through the actions and thoughts of your characters.

Your characters were born in your society: for them, this matriarchal structure is the norm. It will become normal for the reader too, since the reader "perceives" the story through the eyes of the characters (or through your external narrator, if you're using that).

Of course, it will be strange at first: things will happen that the reader won't understand outright. You may open the very first chapter with the fifth marriage of a powerful witch, with the four previous husbands attending the event like it's completely normal.

A mother's brother is considered the true fathers of their children, and spend more time raising them than a biological dad.

So, uncles are the real fatherly figure of your world. You may show how children seek this figure and tend to suffer when it's not there. The term "uncle" doesn't indicate a strong emotional bond and "mother's brother" is a clunky definition, so you could create another term relevant to your society and make characters use it:

Alice: You seem really close with Charlie.

Bob: He's my insert-term-here. Of course I am.

Alice: Ah, I didn't know. I grown up without one and it was a harsh.

Decide a set of core values for your society and keep in mind that they will influence every aspect of day-to-day life. Think your characters accordingly.

Back to the reader: if you do this well, in due time the reader will understand what the basic rules in your story are. He may still think that our society has better cultural norms, of course: but remember that you don't need to convince him.

You just need to explain how things work in your world, be coherent, and he will roll with them.
Being coherent means, for example, that men will more attached to the sons of their sisters rather than their own.

After all what you're trying to do it's not different, let's say, that authors writing about magic, high-tech sci-fi, paranormal events, incredible creatures and so on.

When you meet dragons in a fantasy book you don't jump to the conclusion "Hey, dragons ain't real, they don't exist in this world, how can they be in this story". You just acknowledge they are a thing and go on.

So it's a matter of suspension of disbelief: it will work if you can keep it.

On a side note, I wouldn't struggle to make this alternate society of yours seem like a positive thing. Like most cultural norms, it has upsides and downsides. If you show both equally, you're creating a more believable world, and the reader will be more enthralled by it.

How do you normalize a taboo custom in a setting that most readers would not agree with?

Carefully.

Extramarital affairs and multiple partners are looked down on, and having multiple father's to your children is shameful.

That's it? Not mother-son incest, ripping the beating hearts from your own babies, consuming them with fava beans and a nice chianti??

How do you make it completely normal and a positive thing when the reader most likely has a different experience?

While I agree with @Liquid's basic premise "the reader has to understand that this is not our society", I disagree with his method.

Ignore pre-plot explanations and just dive right in. Your readers should know that they aren't reading a novelization of Leave It To Beaver, and that Things Are Different when there is magic, covens, etc.

Treat matriarchal polyandry as normal, and -- unless you've done something obviously impossible or stupid to break Suspension Of Disbelief (and matriarchal polyandry isn't in and of itself obviously impossible or stupid in this context) -- your readers will, while being a bit puzzled, will plow ahead.

Importantly: drop bits of explanation along the way, as needed.

In reference to the Ursula K. Le Guin comment, the protagonist in The Left Hand of Darkness originates from a familiar societal context to observe an unfamiliar one. The fact that you're "on the journey" with someone from a familar setting and encountering new things along with them could help with assimilation of unfamiliar customs. To varying degrees, nearly every Star Trek episode also put its characters in such a position, so you could (re)watch those for some ideas.

It's possible you'll find some assistance in communities that DO have non-traditional relationship structures. On reddit, you should find helpful commentary in r/nonmonogamy and r/polyamory.

Depends on how disturbing this custom will be seen by an average reader.

In your case, I don't think this custom of a fictitious society will turn away any readers. Just make sure that your protagonist(s) is not advocating it.

But in other cases, a custom may be much more disturbing (ex. cannibalism or marrying off underage girls). There, you need to step carefully, avoiding graphic details (this may depend on your genre, though), and maybe making your protagonist(s) an opponent of this practice.