The main differences between gerbils and mice include their size, tail length, behavior, and care requirements. Gerbils are typically larger than mice, have a long tufted tail, are more social and active during the day, and require a larger habitat with deeper bedding for burrowing. Mice are smaller, have longer tails, are more nocturnal, and are known to be good climbers. Both make popular pets, but it's important to understand their distinct characteristics to provide the best care for each species.