Salidroside (Sal), is one of the important food supplements from the traditional Chinese medicine Integripetal rhodiola herb, encapsulating significant anti-oxidative stress, anti-ferroptosis, and neuroprotective attributes. Notwithstanding these latent virtues, the ramifications of Sal on retinal ganglion cells (RGCs) impairment during the incipient stages of diabetic retinopathy (DR) remain equivocal. The purpose of this study was to investigate inhibitory effect of Sal on ferroptosis of RGCs in db/db mice. Within the research conducted, Sal was administered via gavage, and observations were made 8 weeks post-treatment. Retinal samples were collected for analysis. The results evidenced that Sal ameliorated blood glucose levels, attenuated RGCs destruction, and augmented visual functionality in db/db mice. Additionally, Sal exerted an anti-ferroptosis impact on the RGCs in the db/db mice. Successive discoveries have outlined the involvement of the HIF-1α/HO-1 signaling pathway in this protective mechanism. Ferroptosis of RGCs has a contributory effect on the development of DR, in part through the HIF-1α/HO-1 pathway. Intriguingly, Sal reversed the alterations in the HIF-1α/HO-1 pathway in db/db mice and displayed prospective advantageous effects on DR. Sal mitigated RGCs ferroptosis by reducing blood sugar and impeding the HIF-1α/HO-1 signaling pathway, thereby improving DR. Thus, Sal shows potential for use as a pharmaceutical and nutraceutical for DR.