Every community and society has its peculiar way of life and these practices and beliefs go a long way in influencing the people’s perception, attitude and management of diseases and other health related problems that befall them. The mentally ill in Nigeria are faced with these health challenges which result in some isolating their families and loved ones (nuclear and extended families), while some are rejected due to their cultural beliefs system. Over the years there have been debates on the choice of care for the mentally ill persons because to some the orthodox is preferable to the traditional and vice versa. It’s on this ground that this paper sought to examine the traditional medicine, Orthodox medicine, and the cross cultural care between the traditional and orthodox medicine in the care of the mentally ill persons in Nigeria. The paper also employed the Biopsychosocial model and Holistic model to explain the cross cultural care of mentally ill person(s) in Nigeria. The paper finally justifies itself by employing cross – cultural care for treatment in the tradition and orthodox levels for the mentally ill, describing the psychological distress and associated factors of the attendees of traditional and orthodox healing practices; the prevalence and severity of mental disorders treated by traditional and orthodox practitioners.