Acupuncture with MOK, a polyherbal medicine (MOK pharmacopuncture), has been used for the treatment of thyroid syndromes including hypothyroidism and hyperthyroidism in traditional Korean medicine. The present study investigated the effect of MOK pharmacopuncture on hypothyroidism and the mechanism underlying its antioxidation and immune regulation effects. Hypothyroidism was induced in Sprague-Dawley rats by subcutaneous injection of Propylthiouracil (PTU; 10 mg/kg) once daily for 4 weeks. MOK was administered by acupuncture on the acupoints around the thyroid gland of PTU-induced hypothyroidism rats once daily for 2 weeks following hypothyroidism induction. Administration of MOK pharmacopuncture significantly increased the PTU-induced decrease in body temperature of hypothyroidism rats. The weights of the spleen were also significantly decreased in hyperthyroidism rats following MOK pharmacopuncture. MOK pharmacopuncture significantly decreased the thyroid stimulating hormone level and increased the T3 and T4 levels in hypothyroidism rats. Administration of MOK pharmacopuncture significantly increased the glucose levels and decreased the levels of triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and alanine transaminase in the sera of hypothyroidism rats. The expression of transient receptor potential cation channel subfamily V member 1 was increased in dorsal root ganglion and brain tissues by administration of MOK pharmacopuncture, and glutathione levels and the expression of superoxide dismutase 1 and catalase were increased in the liver and brain tissues. Administration of MOK pharmacopuncture significantly inhibited interferon-γ expression and increased the expression of interleukin (IL)-4, IL-10, and Forkhead Box P3 in the spleen tissues of hypothyroidism rats. In histological analysis, the administration of MOK pharmacopuncture improved the pathological features in the thyroid glands of hypothyroidism rats. The results suggested that the administration of pharmacopuncture may ameliorate the pathological progression of hypothyroidism by multiple actions, including normalization of the hypothyroidism-induced thyroid hormone imbalance, stimulation of the antioxidant defense system, and regulation of the T helper (Th)1/Th2 imbalance. Therefore, MOK extract may be used for the treatment of hypothyroidism in Korean clinics as a useful pharmacopuncture medicine.