The increasing burdens of the world with inflammatory diseases and chronic pains have enhanced the need to have safer, multi-targeted and more effective therapeutic approaches. Polyherbal preparations with their deep-rooted involvement in the traditional systems of medicine are beginning to be viewed as innovative solutions because of their synergetic interactions and holistic action mechanisms. In comparison to the traditional pharmacotherapies, like non-steroidal anti-inflammatory drugs and opioids, which have many side effects, tolerance, and long-term toxicity, polyherbal combinations present a better effect with higher quality and fewer adverse effects and patient adherence. This review is concerned with giving a comprehensive focus on the standardization, phytochemical profiling, and pharmacological validation of polyherbal formulations that have been designed towards the use of anti-inflammatory and analgesic purposes. Phytochemical studies are detailed describing a wide range of bioactive secondary metabolites; flavonoids, alkaloids, phenolic compounds, terpenoids, saponins, among others, that all play a role in their therapeutic efficacy. The quality assessment, fingerprinting, and reproducibility of these complex herbal matrices have been transformed by the use of advanced analytical tools namely HPTLC, HPLC and GC-MS. Pharmacological analyses using in vitro and in vivo models indicate high modulation of inflammatory pathways, blockage of pro-inflammatory products, control of cytokines, and inhibition of oxidative stress pathways. Moreover, such formulations possess the ability to act on a variety of signaling pathways in isolation or in combinations, increasing the therapeutic outcome. Nevertheless, such issues as absence of global standardization procedures, variability of phytochemicals, and the absence of clinical approval are still considerable. The way forward focuses on merging the technology of omics with systems biology and on sound clinical trials to support scientific validity, and provide the conversion of the polyherbal preparations into conventionalized, evidence-based medicine to the contemporary healthcare framework.