Adopting innovative nutritional strategies, such as microalgae blend supplementation, can help reduce the detrimental effects of heat stress (HS) in poultry farming. This study was designed to explore the effects of different dietary levels of microalgae blend containing nannochloropsis oculate, schizochytrium and amphora coffesformis on modulating growth performance, muscle's antioxidant status, lipid profile and the expression of heat shock proteins and sirtuins family related genes in heat-stressed chicks. A total of 250 one-day-old chicks were randomly assigned to five experimental groups, with five replicates of 10 birds each: a control group reared under normal environmental conditions and fed a basal diet; HS group exposed to heat stress and fed a basal diet; and three HS groups supplemented with a microalgae blend at 2.5, 5, and 10 g/kg of diet, respectively. A notable improvement in total growth and FCR especially was recorded in group exposed to HS and supplemented with 10 g/kg diet of microalgae blend compared to HS group. Moreover, the group exposed to HS and fortified with microalgae blend at the concentration of 10 g/kg diet showed reduced cholesterol and triacylglycerol levels, comparable to those of the control group. Notably, all heat-stressed groups supplemented with the microalgae blend showed no significant changes in blood parameters compared to the control group. In the heat-stressed group, dietary supplementation with 10 g/kg of the microalgae blend significantly reduced the levels of ALT, uric acid, AST, creatinine, corticosterone, and thyroid hormones (T3 and T4), bringing them closer to normal physiological ranges. With increasing levels of the microalgae blend, there was a marked enhancement in the activity of muscle antioxidant enzymes, including glutathione peroxidase (GSH-Px), catalase, and superoxide dismutase (SOD), along with an increase in T-AOC content, accompanied by a significant reduction in MDA levels. Notably, increasing the concentration of the microalgae blend resulted in elevated levels of n-3 PUFAs, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the breast muscle. Relative mRNA expression levels of Hsp70, Hsp90, SIRT1, SIRT3, and SIRT7 were elevated in the heat-stressed groups; however, the group supplemented with 10 g/kg of the microalgae blend exhibited the most pronounced downregulation of these genes. In conclusion, this study underscores the potential of the microalgae blend to mitigate the adverse effects of heat stress in poultry farming via modulating antioxidant activity, upregulating expression of sirtuins family and attenuating the overexpression of heat shock proteins.