This study aims to determine the effect of red dragon (Hylocereus polyrhizus) fruit peel extract (RDFPE) on the parameters of Leydig cells number, seminiferous tubules diameter, and testicular weight of mice (Mus musculus) exposed to heat (40°C). Twenty adult male mice were divided randomly into five groups. The control group (C) mice only received a placebo. Meanwhile, the treatment groups mice were exposed to heat for 45 minutes daily for 36 days and oral administration of placebo, RDFPE of 250, 500, and 1000mg/kg BW for T0, T1, T2, and T3, respectively. The result showed that heat exposure on mice (T0 group) caused a lower of all of the parameters (p <0.05) than normal mice (control group, C). RDFPE administration at a dose of 250 mg/kg BW (T1 group) and 500 mg/kg BW (T2 group) resulted in a higher value of those parameters (p <0.05) compared to the T0 group. All those parameters of the T2 group (dose of 500 mg/kg BW) were not significantly different (p >0.05) than the control group (normal mice). However, the higher dose of RDFPE (1000 mg/kg BW, T3 group) resulted in the lower values of those parameters (p <0.05) than those of the T2 group. It could be concluded that 500mg/kg BW dose of RDFPE could return Leydig cells number, seminiferous tubules diameter, and testicular weight of mice (Mus musculus) exposed to heat.