A study was conducted to evaluate the effects of organic acid salt blend (OAB), protease complex (Pr) and their combination (OAB+Pr) in fish meal‐free diets on growth, nutrient retention and digestibility of tilapia. Five diets were designed: a positive control (PC) diet containing 80 g/kg fish meal (FM), a negative control (NC) diet containing 0 g/kg FM and 104 g/kg meat and bone meal, and three other diets supplemented with OAB (922 mg/kg), Pr (175 mg/kg) and OAB+Pr (922 mg/kg + 175 mg/kg) to the NC diet. Tilapia with an initial body weight of 7.0 ± 0.2 g were fed the five diets for 9 weeks. The results showed that the growth performance, nutrient digestibility and retention of NC group had the lowest values among groups. Weight gain of fish fed the OAB and OAB+Pr diets was higher, and feed conversion ratio was lower (p < 0.05) compared to those fed the NC diet, while no differences with those fed the PC diet. The digestibility of dry matter, crude protein, minerals and protein retention was improved in fish fed the OAB+Pr diet (p < 0.05), but not in those fed OAB or Pr diet (p > 0.05). There were no differences in whole‐body composition and lipid retention among the treatments (p > 0.05). The supplementation of OAB and Pr alone or combined significantly increased the villi height but not the width when compared to the NC group. It can be concluded that dietary supplementation of OAB+Pr in a fish meal‐free diet improves growth and nutrient digestibility in tilapia compared to those fed the fish meal‐free diet.