Abstract: Nowadays, natural sources of sex reversal agents are preferred over synthetic ones in fish farming due to their reliability and economic value. This study compared the effectiveness of 17α-methyltestosterone (MT), Carica papaya seed meal (PSM), and common carp testes (CCT) with tilapia (Oreochromis niloticus) in terms of sex reversal, hematological parameters, gonadal histology, enzymatic activity, and overall growth. A 90-day trial was conducted with 560 tilapia fry (2-3 days old) distributed into one control and six treatment aquaria, each with two replicates. Fries were fed with a control diet (T0) or one of six experimental diets (T1-T6) containing different MT, PSM, or CCT levels for 30 days, followed by the control diet for 60 days. MT induced the highest male proportion (85% and 75% in T2 and T1, respectively), while PSM and CCT enhanced tilapia’s growth and carcass composition. Histological analysis revealed gonadal deformities in MT and PSM treatments, which might lead to sterility. The gonadosomatic index (GSI) was reduced in natural treatments as compared with synthetic ones. Hematological parameters did not show any adverse effects of PSM and CCT. Protease and amylase activities were higher in PSM and CCT than in MT, indicating better digestion and feed absorption. PSM and CCT are biodegradable, locally available, and eco-friendly alternatives to synthetic hormones to change sex in tilapia. Natural sources (plant and animal by-products) are preferable to synthetic sources as they are less expensive and control prolific breeding in tilapia.