This research aimed to explore the positive impacts of Ocimum sanctum on Oreochromis niloticus against waterborne cadmium (Cd) toxicity. Total 180 fish (18.41 ± 0.11 g/fish) were distributed into six experimental groups, with three replicates per group, across 18 experimental tanks. Cadmium chloride (CdCl2) was used at a concentration of 3 µg/L. Six treatment groups were: the negative control group, without any supplement or Cd exposure; the positive control group, which received no supplements but exposed to Cd; third group with 10 g/kg supplementation along with Cd 3 µg/L exposure; fourth group with 20 g/kg supplementation along with Cd 3 µg/L exposure; fifth group with 30 g/kg supplementation along with Cd 3 µg/L exposure; and sixth group with 40 g/kg supplementation along with Cd 3 µg/L exposure. The trial lasted for sixty days. Results revealed that waterborne Cd exposure adversely affect the fish growth, body composition, and hematological parameters. However, incorporating O. sanctum considerably increased fish survival and reduced the harmful impacts of Cd. Notably, supplementation at a rate of 30 g/kg improved growth, enhanced carcass quality, and restored blood indices. Ultimately, the results showed that heavy metal toxicity could be successfully mitigated in O. niloticus aquaculture by adding 30 g/kg of O. sanctum as a nutritional supplement. The present findings suggest that the potent bioactive compounds like eugenol and urosolic acid, exhibit antimicrobial, antioxidant, stress-reducing immunostimulant, and hepatoprotective properties in O. sanctum which improve growth, body composition, and hematological parameters while mitigating the effects of Cd toxicity in O. niloticus.