Guinea pigs are a popular companion pet species that are commonly evaluated by veterinarians. However, they often present unique challenges due to their species-specific anatomy, physiology, nutrition, and behavior. This masterclass aims to provide an overview of husbandry, anatomy, physiology, and manual restraint and sedation of guinea pigs. Furthermore, diagnostic sample collection plays an important role in veterinary care, and this masterclass will offer instruction in various techniques including phlebotomy, urine collection, and diagnostic imaging. Drug therapy, critical care interventions, and supportive care strategies will also be discussed. In conclusion, this masterclass will provide attendees with an understanding of how to effectively manage guinea pig patients in clinical settings and improve medical outcomes.