The growing global demand for buffalo meat has heightened concerns about food safety due to the occurrence of chemical contaminants, such as veterinary drug residues, pesticide residues, radioactive substances, heavy metals, and mycotoxins. These contaminants can make way into the food chain through animal feed, environmental exposure, and processing methods, presenting possible health hazards to consumers. To address these concerns, various analytical methods have been devised to detect and quantify chemical residues in buffalo meat. Conventional extraction methods like solid-phase extraction (SPE) and liquid–liquid extraction (LLE) have been widely used, while advanced techniques like QuEChERS, matrix solid-phase dispersion (MSPD), and accelerated solvent extraction (ASE) offer improved efficiency. Chromatographic methods, including gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS), offer high sensitivity and accuracy in detecting contaminants. Additionally, immunoassays and biosensors serve as rapid and cost-effective alternatives for screening residues. Continued research and innovation in analytical technologies, along with stricter monitoring systems, are crucial for minimizing risks and providing safe, high-quality buffalo meat to meet global nutritional demands.