Viper envenomation remains a pressing global health challenge, particularly in tropical and subtropical regions, where access to effective and affordable antivenom therapies is limited. Conventional antivenoms, predominantly derived from animal immunoglobulins, often suffer from limited efficacy, high production costs, cold-chain dependency, and the risk of severe hypersensitivity reactions. This review presents a comprehensive, interdisciplinary analysis of alternative venom neutralisation strategies, focusing on endogenous human proteins and phytochemical inhibitors as novel therapeutic avenues. We explore the mechanistic roles of key endogenous proteins—such as serum albumin, α₂-macroglobulin, tissue inhibitors of metalloproteinases (TIMPs), C-reactive protein (CRP), and antithrombin III—in neutralizing viper venom components, particularly phospholipase A₂ (PLA₂) and snake venom metalloproteinases (SVMPs). These proteins exhibit diverse inhibitory mechanisms, including direct enzymatic blockade, modulation of inflammation, and regulation of coagulation pathways. In parallel, we highlight plant-derived bioactive compounds (phytoligands) such as flavonoids, tannins, alkaloids, and saponins, which demonstrate broad-spectrum inhibition of venom enzymes through antioxidant, anti-inflammatory, and direct enzyme-binding activities. Importantly, this review integrates recent advances in computational biology—molecular docking, molecular dynamics simulations, and AI-driven drug discovery—to elucidate and optimize the molecular interactions between venom components and inhibitors. We emphasize the synergistic potential of combining endogenous proteins with phytoligands to create next-generation, multi-target antivenom therapies that are safer, more accessible, and cost-effective. By bridging biochemistry, ethnopharmacology, and in silico modelling, this review provides a forward-looking framework for developing innovative, non-immunoglobulin-based antivenoms. The insights presented here pave the way for rational drug design and a paradigm shift in snakebite management.