Lack of a cheaper and effective way to produce reproductively sterile fish for better growth to boost production is a big problem that Malawian fish farmers face. This study examined cytotoxic and antifertility effects of Acacia nilotica aqueous pod extracts on Oreochromis shiranus as one way of producing sterile fish. Brine Shrimp Lethality Assay was used to assess cytotoxicity of extracts on concentrations of 0, 20, 40, 60, 80 and 100 mg mL-1. The results showed highest mortality at 100 mg mL-1 concentration (40% mortality) and lowest in 0-40 mg mL-1 (0% mortality). There was no linear component in mortalities of nauplii (p>0.05). Using Meyer’s toxicity index the extract was non-toxic as its LC50 value was 108.95 mg mL-1. An assessment on antifertility effects used four treatments 0, 5, 10, 15 g kg-1 of A. nilotica aqueous pod extract-feed inclusions. Oreochromis shiranus were fed for 16 weeks and reproductive performance was investigated. Gonads developed black spots and atrophy with an increase in inclusion level. Decreasing gonad weight was observed in the following order: 0g kg-1 (0.6±0.07g), 5g kg-1 (0.45±0.08g), 10g kg-1 ( 0.41±0.01g) and 15g kg-1 (0.31±0.04g). As in gonad weight, decreasing motilities were observed in the following order: 6.1±0.23, 4.8±0.05, 3.58±0.14 and 2.31±0.1 minutes respectively. There was a linear relationship in gonad weight and sperm motility with inclusion levels (p<0.05). Testicular histology analysis for control fish showed a high concentration of spermatogenic cysts, normal lumen and interstitial tissue. Testes of fish fed on A. nilotica aqueous pod extract-feed inclusions showed severely depleted with very insignificant amount of spermatozoa, the lumen expanded, interstitial tissue highly shrunk, seminiferous tubules were deshaped, necrosis and vacuolization. Acacia nilotica aqueous pod extract displayed cytotoxicity and antifertility effects in Oreochromis shiranus . Gonadal changes and reduced sperm motility were observed with extract inclusion. This suggests that potential use as a reproductive inhibitor in Oreochromis Shiranus . Further research is needed to assess its effects on female Oreochromis shiranus (Ovaries).