This research study investigated “Drug and substance abuse on the health of street children in Central Division Kisoro Municipality Kisoro District. The purpose of this study was to establish the extent to which drug and substance abuse has affected the health of street children in Kisoro Municipality. The study focused on three objectives which included; to find out the effects of drug and substance abuse on the health of street children, to find out the factors leading to drug and substance abuse among street children and finally to find out the drugs commonly abused by street children in Central division Kisoro District Kisoro Municipality. The study employed descriptive research design where both qualitative and quantitative methods of data collection was used (Questionnaires and interview guide). Collected data was analyzed thematically using tables in form of frequencies and percentages and some graphs. The study found out that the drug and substance abuse had a lot of effects on the health of street children. The effects discovered out of the study included; suicidal thoughts, mental illnesses, depression, verbal abuses, loss of weight and appetite, prolonged illnesses, fights among others. The study furthermore discovered some factors leading to drug abuse which included; idleness, culture, peer influence, mass media, examination pressure and religion. And among the drugs abused include Cannabis, tobacco, Opiates, Nicotine, Cocaine, Marijuana among others. The study therefore recommended that parents should provide enough parental guidance to their children and also encouraging them to attend youth religious camps. The government should also put strict laws regarding drug abuse and alcoholism especially to children as well as taking children practicing drug abuse and alcoholism to rehabilitation centres where they can receive counseling and guidance to reshape their lives hence becoming responsible citizens of the nation