This study evaluated the potential of supplementing sheep diets with cobalt (CoNPs), iron (FeNPs) nanoparticles, or Spirulina platensis (SP) to tackle the adverse impacts of heat stress by assessing growth performance, oxidative status, metabolic pathways, immune parameters, gene expression, and hormone levels in sheep exposed to hot environmental conditions. A total of 32 Rahmani male lambs were randomly divided into four equal groups (n = 8). The CON group was fed the control diet or supplemented with 2 mg/kg of CoNPs (CoNPs group), 50 mg/kg of FeNPs (FeNPs group), or 1 g of SP/kg (SP group) diet for 3 months. The average size of nanozymes CoNPs and FeNPs were 41 and 44 nm, respectively. The temperature humidity index (THI) was 81.99 overall the study period. All nanozyme or SP treatments significantly (P < 0.05) enhanced growth performance, including final and average body weight, and dry matter intake. Nanozyme treatments also achieved the best results regarding hematocrit (P < 0.01) and platelets (P < 0.01). All supplemented groups exhibited lower WBC and lymphocyte counts, and higher globulin levels in comparison to stressed sheep. Total protein levels were significantly (P < 0.001) elevated in the FeNPs and SP groups compared to the remaining groups. Rams fed CoNPs or SP had notably (P < 0.001) higher TC and TG levels, while the FeNPs group showed the lowest TC levels (P < 0.05), as well as the lowest VLDL and LDL levels (P < 0.05). The levels of blood immune markers, specifically lysozyme, IgG, and IgM, were significantly (P < 0.05) elevated in all supplemented groups in comparison to the untreated group. Furthermore, rams receiving FeNPs demonstrated higher (P < 0.05) values for TAC, CAT, SOD, and GPX, and lower MDA levels than the other groups. Additionally, the supplemented group exhibited greater (P < 0.05) leptin and testosterone levels than the stressed group. Further, serum concentrations of zinc, selenium, and iron were significantly (P < 0.05) greater in the nano-feed additives and SP groups compared to the HS group. Dietary supplementation with nanozymes or SP notably (P < 0.05) upregulated GPX1 and HSP70 expression and downregulated TNF-alpha mRNA levels (P < 0.05). In summary, dietary supplementation with nanozymes or microalgae robustly bolstered sheep’s immune-antioxidant capacity, improved growth performance, and promoted health under heat stress conditions relevant to global warming.