Herbal medicine plays an important role in Nigerian society based on its increased patronage. It encompasses the use of naturally occurring, plant-derived substances which are employed to prevent, manage, or treat illnesses. This study was conducted to assess the knowledge, attitude, and practice (KAP) of herbal medicine among the residents of Port Harcourt, Rivers State, Nigeria. A descriptive cross-sectional survey was carried out on 280 residents using self-administered questionnaires comprising demographic information and questions on the knowledge, attitude, and practice of herbal medicine. Data analysis was conducted using SPSS version 21.0 on 244 valid questionnaires. The prevalence of the use of herbal medicine among the respondents was 88.9%, as many (79.1%) believed that best treatment outcomes can be achieved when herbal medicine is used in combination with conventional medicine. Associations between respondents’ demographic characteristics and overall KAP of herbal medicine showed that the level of education and occupation have a significant relationship with the respondents’ practice of herbal medicine. There is a high level of knowledge, attitude, and practice of herbal medicine among residents of Port Harcourt, Rivers State, Nigeria, and education and occupation influence the practice of herbal medicine.