Enzymes are a key part of most metabolic processes and are required for the correct functioning of the human body, either directly or indirectly. Proteolytic enzymes aid in the digestion of proteins in the body. Proteolytic enzymes are created in the pancreas naturally, but they can also be found in certain diets. Serratiopeptidase is an enzyme found in the stomach wall of silkworms and produced from S. marcescens strain. Less solubility, toxicity, instability, incompatibility, and less penetration are all common issues with Serratiopeptidase drug delivery. Because of its proteinaceous nature, serratiopeptidase is susceptible to enzymatic breakdown in the gastrointestinal system. It also has a low permeability through the intestinal barrier due to its hydrophilic nature. Depending on the features of the medicine, a suitable delivery mechanism is required. Topical formulation may eliminate the risk of gastric degradation of drug and increase direct permeation through skin and show effects. Topical SRP may effectively lower inflammatory markers, as it has been found to have superior anti-inflammatory effects than topical NSAIDs. Serratiopeptidase topical formulations could be more effective than nonsteroidal anti-inflammatory medications in treating local inflammation. This article reviews studies on various topical formulations.