Climate change affects aquaculture to a significant extent, while one of the primary threats to Nile tilapia (Oreochromis niloticus) growth and health is suboptimal temperatures. The objective of this study was to assess the effects of Amphora coffeaeformis powder and extract on the growth performance and health status of tilapia grown in suboptimal temperature (21 °C). A total of 180 fish (31.39 ± 0.5 g) were randomly allocated into six groups, each with three replicates. The control group was fed a basal diet. The second and third groups were supplemented with 50 g kg− 1 (AMP50) and 70 g kg− 1 (AMP70) of A. coffeaeformis powder, respectively. The fourth and fifth groups received 50 g kg− 1 (AME50) and 70 g kg− 1 (AME70) of A. coffeaeformis extract, respectively. The sixth group (OXY) was fed a diet with 500 mg kg⁻1 of oxytetracycline. After a 60-day feeding trial, all fish were challenged with Aeromonas sobria. The findings indicated that the extract of A. coffeaeformis, particularly at a concentration of 70 g kg− 1 diet, significantly enhanced growth performance, hematological and biochemical parameters, antioxidant and immunological markers. Additionally, it notably increased resistance against A. sobria. These results suggest that A. coffeaeformis supplementation, particularly AME at 70 g kg− 1, effectively mitigates suboptimal temperature effects on Nile tilapia productivity by enhancing growth, health, and disease resistance.