Momordica charantia polysaccharide (MCP) is a potential drug for the prevention and alleviation of diabetes mellitus (DM) and diabetic retinopathy (DR). This study aimed to investigate the potential protective effects of MCP on early-stage DR and explore the underlying mechanisms. The model group (DM group) and treatment group (D+H group) were established by inducing type 1 DM using a single dose of streptozotocin (STZ) at 60 mg/kg. After modeling, the D+H group was orally administered a 500 mg/kg dose of MCP solution once daily for 12 weeks. Monitoring of systemic indicators (FBG, body weight, general condition) and retinal tissue inflammation and apoptosis (HE staining, IL-6, MCP-1, TNF-α, VEGF, NF-κB, Caspase-3) in this study demonstrated that MCP intervention alleviated both DM and DR. MCP improved the body weight and general condition of DM rats by reducing FBG levels. It also enhanced the anti-inflammatory and anti-apoptotic capabilities of retinal neurons and microvessels by modulating the actions of cytokines, thereby further regulating the inflammation and apoptosis of retinal neurons and microvessels. The underlying mechanisms may be associated with the downregulation of NF-κB and Caspase-3 pathway protein expression, as well as the downregulation of mRNA expression of NF-κB and Caspase-3 pathway genes. Further research is needed to elucidate the potential mechanisms underlying the protective effects of MCP on DR. MCP may emerge as a selective medication for the prevention and alleviation of DM and a novel natural medicine for the prevention and alleviation of DR.