In the present study, we investigated the protective effect of syringic acid (SA) loaded silver nanoparticles (AgNPs) on endoplasmic reticulum stress-mediated apoptosis during ovarian ischemia-reperfusion injury (IR) in rats. Initial UV–Vis and FT-IR analysis revealed the presence of the Ag and SA in the SA-AgNPs, respectively. TEM analysis demonstrated the spherical morphology with 10–50 nm of nanoparticle size. Next, we evaluated the protective effect of SA-AgNPs against IR. 15-weeks-old rats were divided into seven groups, as follows: control, AgNPs, SA, IR, AgNPs + IR, SA + IR, and SA + AgNPs + IR. Induction of IR led to a significant increase in apoptotic markers (caspase-3), pro-inflammatory markers (IL-1β, TNF-α, ATF-6, NF- κB-p65, and P2X7R), and endoplasmic reticulum stress marker (IRE1) in ovary tissue. Additionally, a remarkable increase in serum IL-1β and TNF-α were found. Moreover, an increase in serum MDA and decreased endogenous anti-oxidant enzymes, including GSH and SOD were observed. Interestingly, treatment with either AgNPs or SA significantly reduced apoptosis, inflammation, and ER stress markers in IR-induced rats. Nevertheless, discernible effects were detected in rats upon treatment with SA + AgNPs. These findings strongly suggest that syringic acid-loaded silver nanoparticles have a promising therapeutic application in ovarian ischemia-reperfusion (IR) injury.