The entire soundtrack for this game uses no instruments other than human voices, provided by A Cappella group, Spiralmouth.
Clancy Brown was originally offered to come back to voice Cortex, but declined as he felt he was not fairly compensated for his work on the previous Crash Bandicoot games. This also gave Vivendi Universal the opportunity to give Cortex a more comedic voice, as parents complained that Clancy Brown's voice made Cortex too scary for their children.
The Evil Twins were based on the Lead Concept Artist's girlfriend's two hateful cockatoos.
Before Crash Bandicoot 4 was made, Twinsanity was considered by many to be the last good game in the Crash Bandicoot series, not counting the 2017 remake of the original PS1 Trilogy.
An altogether different game was originally planned, until its concept was scrapped. Its name was Crash Bandicoot Evolution. Much of the concept art for this game can still be found in Twinsanity's Yellow Gem Extras. The reason why it was scrapped was because the game's story was similar to that of Ratchet and Clank.