Drug analysis in biological samples remains a significant challenge due to the complex matrix composition that can interfere with extraction and detection processes. The QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method, initially developed for pesticide residue analysis, has been increasingly adapted for forensic toxicology, particularly in drug extraction from biological matrices. This review explores various modifications of the QuEChERS method applied to blood, urine, and liver samples, focusing on the effectiveness of different solvents, buffer salts, and sorbents in enhancing extraction efficiency. Furthermore, it highlights current challenges such as matrix effects and the critical importance of method validation to ensure reliability and reproducibility. By analyzing recent developments and trends in QuEChERS applications, this review offers valuable insights into optimizing extraction protocols for forensic purposes. The findings aim to support the advancement of more efficient, robust, and accessible analytical techniques in forensic toxicology, ultimately contributing to more accurate and reliable drug detection in complex biological samples.