| Summary: | <i>Salsola cyclophylla</i>, an edible halophyte, is traditionally used for inflammation and pain. To confirm the claimed anti-inflammatory and analgesic properties, a detailed study on respective pharmacological actions was undertaken. The activities are contemplated to arise from its phytoconstituents. The LC-MS analysis of <i>S. cyclophylla</i> 95% aqueous-ethanolic extract revealed the presence of 52 compounds belonging to phenols, flavonoids, coumarins, and aliphatics class. A high concentration of Mn, Fe, and Zn was detected by atomic absorption spectroscopic analysis. The ethyl acetate extract showed the highest flavonoid contents (5.94 ± 0.04 mg/g, Quercetin Equivalents) and Fe2<sup>+</sup>-chelation (52%) potential with DPPH radicals-quenching IC<sub>50</sub> at 1.35 ± 0.16 mg/mL, while the aqueous ethanolic extract exhibited maximum phenolics contents (136.08 ± 0.12 mg/g, gallic acid equivalents) with DPPH scavenging potential at IC<sub>50</sub> 0.615 ± 0.06 mg/mL. Aqueous ethanolic extract and standard quercetin DPPH radicals scavenging’s were equal potent at 10 mg/mL concentrations. The aqueous ethanolic extract showed highest analgesic effect with pain reduction rates 89.86% (<i>p</i> = 0.03), 87.50% (<i>p</i> < 0.01), and 99.66% (<i>p</i> = 0.0004) after 60, 90, and 120 min, respectively. Additionally, aqueous ethanolic extract exhibited the highest anti-inflammation capacity at 41.07% (<i>p</i> < 0.0001), 34.51% (<i>p</i> < 0.0001), and 24.82% (<i>p</i> < 0.0001) after 2, 3, and 6 h of extract’s administration, respectively. The phytochemical constituents, significant anti-oxidant potential, remarkable analgesic, and anti-inflammatory bioactivities of extracts supported the traditionally claimed anti-inflammatory and analgesic plant activities.
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