In the past decade, the rise of multidrug-resistant bacterial strains has limited the use of conventional antibiotics in the pharmaceutical and food industries, thereby exposing a significant worldwide health concern. On account of this, antimicrobial peptides (AMPs) are documented as broad-spectrum antimicrobials and have attracted particular interest as prospective alternatives to conventional pharmaceutical formulations and food preservatives. Casein, the most prevalent protein family in milk, has been cited as an indispensable source of bioactive peptides. In consequence, this chapter describes the various in vitro and in silico techniques used to extract and validate casein-derived AMPs. In addition, this chapter provides a detailed analysis of all previously described casein-derived AMPs, hence allowing the identification of the key AMP sources and the corresponding production and release mechanisms and strategies. Finally, solutions based on deep learning are proposed as viable and effective alternatives to the current AMPs-discovery methodologies.