Palmoplantar pustulosis (PPP) is an autoinflammatory dermatosis that causes recurrent blisters and aseptic pustules on the palms and soles, affecting patients’ quality of life. This report describes a case of a 62-year-old woman who suffered from PPP resistant to a combination therapy, including steroid ointments over ten years. She was overweight and hypertensive, with a history of smoking, sinusitis and periodontal disease as risk factors for PPP development. At her first visit to our clinic, aseptic pustules, resultant scaly lesions and bleeding from cracks on both palms and plantar surfaces were observed. Coexisting Hashimoto’s thyroiditis was found along with liver dysfunction, a high titer anti-nuclear antibody (1:1280) and an elevated blood eosinophil count. In Kampo diagnosis, she was a yang and excess pattern with blood heat. Orengedokuto and Byakkokaninjinto ameliorated her skin lesions, assessed by PPP Area and Severity Index (PPPASI) decreasing from 28.4 at initiation of treatment to 9.6 at 16 weeks. Body weight, blood pressure, liver enzymes levels and blood eosinophil count also decreased. It has been reported that orengedokuto exerts immuno-suppressive effects, while byakkokaninjinto has anti-allergic effects and an inhibitory effect on itch in animal models. Also, anti-anxiety actions of the components in orengedokuto may have helped her out of binge-eating habit and resulted in weight loss. Formula to clear blood heat may become an effective treatment for PPP associated with autoimmune diseases.