Objective To investigate the correlation between serum leucine-rich α-2 glycoprotein 1 (LRG1) and fibroblast growth factor 21 (FGF-21) levels and neovascular glaucoma (NVG). Methods A total of 110 patients with NVG admitted to the ophthalmology department from September 2020 to September 2022 were selected as the NVG group (23 patients of grade II, 44 patients of grade III, 43 patients of grade IV), 90 cataract patients matched with sex and age were the control group. The levels of LRG1, FGF-21, VEGF, PEDF and TNF-α in serum were detected by ELISA; Pearson correlation analysis was used to analyze the correlation between serum LRG1, FGF-21 levels and Teich grade, VEGF, PEDF, TNF-α levels. Results The levels serum LRG1, FGF-21, VEGF, PEDF and TNF-α in NVG group were obviously higher than those in control group (P<0.05). With the increase of Teich grading, the levels of serum LRG1, FGF-21, VEGF, PEDF and TNF-α in NVG patients increased obviously in turn, and there was a statistically obvious difference between the subgroups (P<0.05). Correlation analysis showed that the levels of LRG1 and FGF-21 in serum of NVG patients were positively correlated with the levels of VEGF, PEDF and TNF-α (P<0.05). Conclusion The levels of LRG1 and FGF-21 in serum of patients with NVG are obviously increased, which are positively correlated with the levels of VEGF, PEDF and TNF-α, and may cooperate with VEGF, PEDF and TNF-α to induce the occurrence and development of NVG.