This study investigates the comparative effects of the chemical pesticide deltamethrin and the biopesticide neem extract on the climbing perch (Anabas testudineus) by assessing biochemical parameters, histological changes, and DNA damage using the comet assay. Deltamethrin, a widely used synthetic pyrethroid, is known for its high efficacy against pests but also poses significant risks to aquatic life. Conversely, neem extract, derived from the neem tree (Azadirachta indica), is considered a safer alternative due to its biodegradability and lower toxicity to non-target species. The results of this study indicated that deltamethrin exposure led to significant increases in stress protein levels, liver enzyme activities, along with pronounced histological damage in liver tissue. In contrast, neem extract exposure resulted in comparatively lower biochemical and histological alterations. The comet assay revealed higher DNA damage in fish exposed to deltamethrin compared to those treated with neem extract. These findings suggest that while both pesticides impact the health of climbing perch, neem extract poses a lower risk of biochemical and genetic damage. This study underscores the need for adopting biopesticides like neem extract to mitigate the adverse effects on non-target organisms associated with chemical pesticides.