Inflammation involves various interlinked pathways and processes. In its uncontrolled form, inflammation results in variety of diseased sates. Current therapy for inflammatory diseases is limited to steroidal and non-steroidal anti-inflammatory drugs (NSAIDs). But these are associated with safety concerns and have a deleterious effect on wound healing. Proteolytic enzymes, also called proteases, which are naturally occurring substances derived from animal or plant sources, are believed to be effective and safer alternatives to the conventional medications. Combined with the bioflavonoid rutoside, the proteases trypsin and bromelain have been extensively investigated as alternatives to conventional therapies for pain and swelling associated with diverse conditions. Their individual mechanisms of action and the advantages of combining bromelain and rutoside with trypsin has been discussed. The combination not only covers a wider range of processes involved in inflammation, but they also complement each other’s actions and provide a more well-rounded control of the inflammatory processes.