The study investigated the effects of Xin'an Jianpi Tongbi Formula (XAJPF), composed of Huangqin Qingre Chubi Capsule and Xinfeng Capsule, on patient self-perception (SPP) and systemic inflammation in 935 patients with rheumatoid arthritis from August 2023 to February 2025. Patients were grouped according to neutrophil-to-lymphocyte ratio (NLR) and XAJPF exposure (high/low). A higher inflammatory state was associated with a worse SPP score. XAJPF exposure improved SPP scores and inflammation levels (NLR, SIRI) without liver or kidney damage. Logistic regression showed XAJPF as an independent protective factor against deterioration of PF, GH, VT, MH, VAS, PGA, PhGA, CPRI-RA, SDS, SDH, and SDSSD parameters with odds ratios of 0.24 to 0.60 (all P<0.05). NLR and SIRI mediated 5.1 to 14.4% improvement on VAS, PhGA and SDSSD scores. Subgroup and sensitivity analyzes confirmed the robustness of the effects. The study confirms NLR and SIRI as partial mediators of the therapeutic effects of XAJPF in RA.