Growing mixed-sex Nile tilapia, Oreochromis niloticus in earthen ponds to table size is a major challenge due to its early maturity and prolific breeding. This study determined the effects of two medicinal plants; Aspilia plant, Aspilia mossambicensis and Neem tree, Azadirachta indica on hatchlings production, growth performance, feed utilization, survival and haematology of O. niloticus. Experimental diets were prepared by adding 1.0, 2.0, 4.0 and 8.0 g of either A. mossambicensis or A. indica leaf powders into a kg of the control diet subsequently administered daily to twenty triplicates of O. niloticus for three months. Both A. mossambicensis and A. indica leaf powder at the used doses, reduced significantly hatchlings production of O. niloticus when compared to the control (P < .05). The lowest value of hatchlings count was found in A. indica dose 8.0 g kg−1 (P < .05). The use of A. mossambicensis leaf powder at a dose of 4.0 g kg−1 improved significantly growth performance and feed utilization (P < .05). In contrast, survival rate was not affected significantly by the two plants (P > .05). Both plants differentially increased significantly haematological parameters such as Hb concentration, packed cell volume (PCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cells (WBC), monocyte and lymphocytes while reduced significantly neutrophils and eosinophils (P < .05). In conclusion, A. mossambicensis and A. indica leaf powders control prolific breeding of O. niloticus, modulate its growth performance and feed utilization. The two plants also modulate haematological parameters of O. niloticus indicating immunological response towards stress or intoxication, however, the values obtained were not beyond the recommended range for healthy fish.The Government of United Republic of Tanzania through the Tanzania Commission for Science and Technology (COSTECH)