The effects of different capsaicin doses were investigated for the alleviation of gastrointestinal inflammation in mice under low-temperature and low-humidity conditions. Mice were randomly divided into control, low-temperature and low-humidity model, and capsaicin-treated groups (10, 15, 20 mg/kg) for a 7-day test period. The body weight of the mice was recorded, and the histopathological changes in the stomach and duodenum were observed. The serum levels of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interferon-γ (IFN-γ) were detected. NF-κBp65, IκB-α, IL-1β, and TNF-α expression levels, along with other mRNAs and proteins, were measured in gastric and duodenal tissues. A low-temperature and low-humidity environment significantly decreased the body weight of mice, significantly increased serum levels of inflammatory factors, significantly upregulated inflammatory factor gene expression in gastric tissues, and significantly downregulated NF-κBp65 protein levels in duodenal tissues. Capsaicin treatment at 15 mg/kg significantly increased body weight and decreased serum levels of inflammatory factors in mice. Capsaicin treatment down-regulated the expression of inflammatory factors in gastric tissues and significantly upregulated key pathway protein expression in duodenal tissues to restore normal levels. The results imply that capsaicin consumption (10~20 mg/kg) under low-temperature, low-humidity conditions (10 ℃, 30%) could alleviate gastric mucosal damage and restore duodenal villi breakage, providing guidance for healthy consumption of chili peppers under low-temperature and low-humidity conditions.