The prevalence of chronic periodontitis (CP), a pervasive chronic inflammatory condition, is significantly influenced by genetic predisposition. This investigation probes the association between CP and polymorphisms in genes encoding anti-inflammatory and immune response mediators—namely TNF-α, MMP-2, MMP-9, TIMP-2, and IL-13—among the Li ethnic group in Hainan Province. These genes are pivotal in modulating the immune response to periodontal infection, which, beyond oral health, may impact physical fitness and mental well-being, particularly in athletes. Our study encompassed 175 CP patients (75 from the Li ethnic group and 100 from the Han ethnic group) and 122 ethnically matched controls (100 Li and 22 Han individuals), focusing on five single nucleotide polymorphisms (SNPs): TNF-α-308A/G, MMP-2-1306C/T, MMP-9-1562C/T, TIMP-2-418G/C, and IL-13-1112C/T. Genomic DNA was genotyped from buccal swabs using the Snap shot method. Our findings revealed no significant association between the studied SNPs and CP in both the Li and Han populations (P>0.05), indicating these genetic markers may not influence CP susceptibility in these groups. This suggests that while these SNPs are not directly linked to CP among the Li ethnic group, the broader implications for physical fitness and mental health in athletes warrant further exploration, considering the interconnectedness of systemic and oral health.