Background The misuse of illicit substances is associated with increased morbidity and mortality; thus, substance abuse is a global health concern. The Arabian Gulf region is considered a crossing point and a consumer of illicit drugs. However, a lack of laboratory-based research has limited the scientific assessment of drug misuse in the Arabian Gulf region. Thus, an up-to-date analytical representation of the drug situation is warranted. Methods We investigated the type and quantity of detained narcotic drugs and psychotropic substances from 2015 to 2018, representing a population of approximately 4 million people, in addition to the number of abusers and mortality among abusers. In total, 6220 cases from the Narcotic and Psychotropic Laboratory and 17,755 cases from the Forensic Toxicology Laboratory were reviewed and analyzed. Substances were identified and documented using gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry. Results Cannabis, including marijuana, was the most seized substance, followed by heroin, opium, and cocaine. Amphetamines, including methamphetamine, in the form of powder or pills, were seized in larger quantities than other psychoactive substances. The most consumed substances were, in order, amphetamines (including methamphetamine), benzodiazepines, cannabis, and heroin. We identify the common drugs in postmortem specimens, according to sex, from suspected drug-related deaths. The most common single drug identified were heroin, benzodiazepines, and methamphetamine. Similarly, the multiple-drug cocktail of heroin–benzodiazepines, cannabis–benzodiazepines, and cannabis–amphetamines, were detected frequently. Conclusions The data shows that cannabis is the leading type of illicit substance seized. Deaths resulting from benzodiazepines and heroin abuse were the highest in the single drug category, while heroin-benzodiazepines combination deaths were the highest in the multiple-drug category. Methamphetamine was the most abused illicit drug in Kuwait. These findings revealed the illicit drug abuse situation in the State of Kuwait, in a region that suffers from the scarcity of information regarding illicit substances. Thus, providing valuable information for drug enforcement, forensic analyst, health workers on national and international levels.