The basic cause of ischemia/reperfusion (I/R) injury is well recognized to be a cell damage resulting from the presence of reactive oxygen species. The objective of this research was to examine the impact of morin hydrate on skeletal muscle-I/R damage. To generate the I/R model, a tourniquet was applied to the hindlimbs of Sprague-Dawley rats. Subsequently, the animals were randomly allocated into four distinct groups. In comparison to the sham group, an elevation in malondialdehyde (MDA) levels was observed in the context of I/R injury. Conversely, the administration of morin exhibited a dose-dependent reduction in MDA levels. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), as well as the levels of reduced glutathione (GSH), were seen to rise in the context of I/R damage. However, with administration of morin, these parameter values exhibited a tendency to approach those of the control group. In the context of I/R damage, it was shown that the expression of Nrf-2 and HO-1 genes was down regulated. However, the injection of morin resulted in the upregulation of these genes. While MPO expression levels increased in the I/R group, they decreased in the morin-treated groups. The gene expressions of NF-κB, IL-1β, TNF-α, iNOS, COX-2, STAT3, and MAPK 14 were seen to be elevated in ischemia/reperfusion (I/R) injury group. Conversely, in the I/R + Morin 100 group, these gene expressions were notably reduced (P<0.001). The study revealed that morin had an upregulatory effect on the expression of Bcl-2 protein, while concurrently downregulating the expression of caspase-3 and Bax proteins. The study revealed a reduction in ICAM1 level and beclin-1 activity in the I/R group, particularly in the I/R + Morin 100 group. The findings of our study indicate that morin has a protective effect against skeletal muscle I/R damage via its ability to modulate the antioxidant defense system and inhibit apoptosis, autophagy, and inflammation.