Abstract: Background and Objective: In recent years, many studies have tended to use herbal plants instead of drugs in fish farms, because they are safer and cheaper. This study aimed to compare the use of17α-methyltestosterone (17α-MT), pawpaw (Carica papaya) seeds powder (PSP) and neem (Azadirachta indica) leaves powder (NLP) as reproductive controller agents for Oreochromis niloticus. Materials and Methods: This experiment was divided into 2 consecutive periods, the 1st period was the treating period with dietary 17α-MT, PSP and NLP for 60 days. Then, the 2nd period was conducted for rearing the obtained fingerlings till the adult stage for 130 days. The treatments were (T1) hormone untreated mixed-sex fry, (T2) fry treated with 60 mg 17α-MT kg–1 diet for 28 days, (T3) fry treated with 6 g PSP kg–1 diet for 45 days and (T4) fry treated with 1 g NLP kg–1 diet for 60 days. Results: Fish treated with 17α-MT gave the highest significant values of growth performance, highest male percentage and economic efficiency followed by PSP, then NLP compared to the mixed-sex group. While, fish treated with PSP were the worst significantly effects on sperm quality parameters. Hence, it could be concluded that addition of PSP improved growth performance, food efficiency and economic efficiency of O. niloticus nearly the same results were obtained by using 17α-MT. Conclusion: This means it is recommended for using PSP as a natural reproductive controller agent for O. niloticus, besides its prospective economically and safety effects on fish environment, production and human health than using 17α-MT.