In order to investigate the synergistic improving effect of lutein (LUT) and epigallocatechin-3-gallate (EGCG) treatment on retinitis pigmentosa (RP), an N-methyl-N-nitrosourea (MNU)-induced mouse model was conducted in the present study. Compared to the LUT alone treatment group, in the LUT combined with EGCG (LUT-EGCG) treatment group, the accumulation content of LUT was significantly increased by 50.24% in the liver. The morphological results indicated that LUT-EGCG treatment significantly improved the retina structure with the thickness of the outer nuclear layer restored to 185.28 ± 0.29 μm, showing no significant difference compared to the control group. The LUT-EGCG treatment also increased the production of short-chain fatty acids, such as acetic and propionic acids. Compared with the LUT alone treatment, the LUT-EGCG treatment significantly increased the relative abundance of Lachnospiraceae and Helicobacteraceae. RT-qPCR results indicated that LUT-EGCG treatment significantly increased the antiapoptotic gene Bcl-2 expression. In addition, the expression of IL-6 was significantly down-regulated in the LUT-EGCG group, while there was no significance in NF-κβ, TNF-α, IL-1β, and IL-18 compared with the LUT group. Correlation analysis supported the conclusion that LUT combined with EGCG may improve RP by modulating antiapoptotic gene expression and regulating the abundance of gut microbiota. However, the underlying mechanism still needs further research.