Background and objectives: Precocious maturity of Oreochromis niloticus results in overpopulation of fish enclosure and eventually poor growth and production rate hence the need to control its reproduction for better harvest. The specific objectives of this study were to: assess the nutrient utilization of Oreochromis niloticus fed Martynia annua leaf meal, determine the effect of feeding Martynia annua leaf meal diets on the reproductive performance (milt count, testis weight, ovary weight and fecundity) of both male and female Oreochromis niloticus, analyze the anti-fertility effects on the histology of testis and ovary of Oreochromis niloticus and evaluate the effect of increasing dietary levels of Martynia annua leaf meal on the histology of the liver and gills. Materials and Methods: The effect of feeding Martynia annua leaf meal for 72 days on the reproductive performance of Oreochromis niloticus (average weight; 10.87±0.50 g) was studied. Five treatments [0, 20, 40, 60 and 80 g kg1 Martynia annua leaf meal (MALM)] with three replicates were used. Plastic tanks (75×45×25 cm) with 30 L capacity were filled with well water of 20 liters and 15 Oreochromis niloticus were introduced into each tank. The fish were fed at the rate of 4% of body weight two times a day at 9:00 and 17:00 h. Results: A reduction in milt count and fecundity was observed as the MALM increased in the diets of Oreochromis niloticus. In all the treatments, there were significant differences (p≤0.05) in pH and dissolved oxygen of the water used. The histology of the testis of Oreochromis niloticus fed 0 g and 20 g kg of MALM showed primary and secondary spermatogonia in the lumen of the seminiferous tubule while the fish fed 40 g, 60 g and 80 g kg1 of MALM showed necrosis, abnormal gonadal development and increase in interstitial cell. The histology of the ovary in fish fed 0 g kg1 MALM showed yoke droplets while the ones fed 20, 40, 60 and 80 g kg1 MALM showed developing oocyte, necrotic oocyte, increase in interstitial cell and alteration in ovary development respectively. The liver showed normal hepatocellular architecture in fish fed 0 g of MALM kg1 and increase in interstitial cell in fish fed 20 g kg1 MALM, increase in portal vein in fish fed 60 g kg1 MALM and severe degeneration in the hepatocytes architecture in the fish fed 80 g kg1 MALM. Conclusion: The histological observation and milt analysis revealed that Martynia annua leaf meal is very effective fertility inhibitor in Oreochromis niloticus reproduction. Moreover, the inclusion of Martynia annua in the diet did not inhibit the growth performance of Oreochromis niloticus.