Missy's parents, Cyrus and Monica, are played by Jordan Peele and Chelsea Peretti, who are married in real life.
Nick and Andrew are based off of the show's co-creators Nick Kroll and Andrew Goldberg, and much of the show's content reflects real events from their life. The other cast members also often served as inspiration for their respective characters. For example, Jenny Slate used to be quite small and wore overalls, like her character Missy, until one senior student came up to her and yelled to her: "Why do you look like a baby?"
Nick Kroll voices up to twelve characters, including Nick Birch, Maurice the Hormone Monster, and Coach Steve.
During the Electric Slide number at Jessi's Bat Mitzvah, Matthew is seen and heard doing lots of vocal runs and singing dramatically in the background. Andrew Rannells, who plays Matthew, is a popular Broadway star who is known for singing overly dramatic showstoppers.
During filming of the second season, Netflix renewed the show for a third season.