Mastitis is an inflammatory disease that deteriorates the quality and quantity of milk, leading to poor performance and economic losses for the county's dairy farmers. Platelet-rich plasma (PRP) is a value-added product of blood that contains higher levels of platelet count in comparison to the blood. Platelets secrete growth factors that could positively impact clinical circumstances, needed speedy healing, and proper tissue regeneration. The extended usage of antibiotics is leading to serious health-associated concerns, such as drug residues in milk and milk products, and elevated trends of resistance to antibiotics. Considering the scenario, it is aimed to find a different management plan for mastitis using PRP as an alternative treatment option. Platelet Rich Plasma (PRP) is an alternative therapy for the treatment of Bubaline Mastitis. For this purpose, three treatment groups, i.e., the antibiotic group, the antibiotic and PRP group, and the PRP group, were evaluated. The data concluded that PRP, independently and along with judicious use of antibiotics, could be a helpful management option to address the inflammatory response and microbial adherence to the lining of udder tissues. Correlation and regression analysis also concluded a significant relationship between antibiotics and PRP. Optimization via response surface methodology also concludes that certain antibiotics at their recommended doses, along with PRP treatment, significantly reduce Bubaline mastitis in buffaloes. This study may be replicated in other domestic animals, such as sheep and goat, to evaluate their efficacy against mastitis to enhance the usage of PRP in different species.