The immunomodulatory properties of kolaviron (KV), a mixture of three related biflavonoids of Garcinia kola Heckel (Clusiaceae), were investigated. The study was conducted using in vitro and in vivo immunocompetent and immunocompromised animal models. KV (250 and 500 mg/kg) produced a dose-dependent and significant (p < 0.05) inhibition of delayed-type hypersensitivity in rats and also caused a significant (p < 0.05) increase in the primary and secondary sheep erythrocytes-specific antibody titres in rats. In vitro, KV inhibited the classical complement system at concentrations greater than 100 microg/ml. The administration of KV ameliorated the cyclophosphamide-induced leukopenia and increased the proportion of lymphocytes count in rats after 14 days of treatment. Administration of KV on alternate days after immunosuppression with cyclophospamide increased the rate of excision wound closure and reduced epithelialization period from 21.75 to 15.5 days. This study established the immunomodulatory and immunorestorative properties of KV, which could be harnessed for possible clinical benefits to immunodeficient patients.