A systemic inflammatory response via host-tumor interactions is a cancer hallmark that plays a pivotal role in the pathogenesis of malnutrition and sarcopenia in patients with malignancies. Hochuekkito (TJ-41) is a traditional Japanese herbal medicine that modulates inflammation in patients with various chronic inflammatory diseases. However, the clinical efficacy of TJ-41 in patients with malignancies remains unclear. We systemically analyzed chronological changes in levels of systemic inflammatory parameters, nutrition-related parameters, and body composition status in 99 patients who received TJ-41 treatment for more than 3 months. The cohort comprised 56 patients with gastrointestinal cancer (Cancer Cohort) and 43 with other diseases (Other Disease Cohort). We also performed invivo experiments in mice to validate the clinical findings. Despite no significant changes in serum albumin concentration and prognostic nutrition index, the serum C-reactive protein (CRP) concentration significantly decreased in a time-dependent manner in all patients. However, the serum CRP concentration significantly decreased during TJ-41 treatment in the Cancer Cohort but not the Other Disease Cohort. Furthermore, downregulation of CRP during TJ-41 treatment occurred only in patients with metastases. The psoas muscle index, as a muscle quantity marker, was significantly lower in the CRP-increased group compared with the CRP-decreased group during TJ-41 treatment. Invivo experiments using a Colon-26 syngeneic model showed that the plasma CRP, amyloid A, and interleukin-6 concentrations were significantly lower in the TJ-41 group than the control group. TJ-41 might be useful as part of multimodality therapy for gastrointestinal cancer, especially in patients with metastases.