Traditional Indian medicine (Ayurveda) has a long history of treating central nervous system (CNS) disorders. Ayurvedic plants are typically rich in flavonoids, lignans, sterols, tannins and alkaloids that exert potent anti-inflammatory, anti-oxidant, neuroprotective and neurotropic effects in both humans and rodents. The zebrafish (Danio rerio) has emerged as a useful model species and a powerful vertebrate in vivo system for CNS disease modeling and drug screening. As zebrafish continue to demonstrate their growing utility for studying a wide range of pharmaceutical therapies, including Chinese and American traditional medicines, here we discuss CNS effects of various Ayurvedic medicinal plants, and how they can be further elucidated using zebrafish models. We also evaluate the existing challenges and limitations of using zebrafish models for studying Ayurvedic pharmacotherapy, as well as outline future directions of translational research in this field.