Parkinson’s disease is the second most common neurodegenerative disease after Alzheimer’s disease characterized by early degeneration of dopaminergic neurons in the substantia nigra pars compacta and accumulation of Lewy bodies. Parkinson’s disease is traditionally known to be associated with motor symptoms; however, it is also associated with non-motor symptoms like pain which may precede motor symptoms by more than a decade. Therapy for Parkinson’s disease primarily involves the use of levodopa which is linked to polyneuropathy and predominantly targets motor symptoms neglecting the non-motor symptoms cold hypersensitivity. The aim of the study was to investigate the effect of Cannabidiol (CBD) and Tetrahydrocannabinol (THC) on Cold Hypersensitivity in reserpine induced Parkinson’s disease in mice. Forty-two (42) mice were randomly divided in to seven groups of six mice each. Group I was the control group that were administered distilled water (10 ml/kg). Group II received reserpine (0.5 mg/kg), Group III received reserpine (0.5 mg/kg) and Cannabidiol (CBD) (30 mg/kg), Group IV received reserpine (0.5 mg/kg) and CBD (60 mg/kg), Group V received reserpine (0.5 mg/kg) and; Tetrahydrocannabinol (THC) (4 mg/kg), Group VI received reserpine (0.5 mg/kg) and; Tetrahydrocannabinol(THC) (6 mg/kg) and Group VII received reserpine (0.5 mg/kg) and; CBD (60 mg/kg) +THC (6 mg/kg). All administration were carried out intraperitoneally for three weeks. Cold pain threshold increased significantly (P < 0.05) in reserpine (0.5 mg/kg) + CBD (60 mg/kg) and reserpine (0.5 mg/kg) + THC (6 mg/kg) groups. Malonaldehyde (MDA) concentration decreased significantly in the reserpine (0.5 mg/kg) + CBD (30 mg/kg), reserpine (0.5mg/kg) + THC (4mg/kg) and reserpine (0.5 mg/kg) + CBD (60 mg/kg) +THC (6 mg/kg) treatment groups respectively. Superoxide dismutase (SOD) concentration increased significantly (P < 0.05) in reserpine (0.5 mg/kg) + CBD (60 mg/kg), reserpine (0.5 mg/kg) + THC (6 mg/kg) and reserpine (0.5 mg/kg) + CBD (60 mg/kg) +THC (6 mg/kg). Reduced glutathione level (GSH) increased significantly (p < 0.05) in reserpine (0.5 mg/kg) + THC (6 mg/kg) and reserpine (0.5 mg/kg) + CBD (60 mg/kg) + THC (6 mg/kg) groups. In conclusion, CBD and THC were able to improve cold pain threshold and at the same time decreasing MDA concentration and increasing SOD activity and GSH concentration.