Salsola is one of the largest and most important genera in the family Chenopodiaceae. Salsola species are used for their anti-inflammatory, antinociceptive, anthelmintic and antipruritic effects and also as diuretic in traditional medicines worldwide. The aim of the present study is to assess the activity potential of the extracts, subextracts and isolated compounds from the aerial parts of and Salsola grandis, an endemic species in Turkey in a scientific platform. The effects of the extracts, subextracts and isolated compounds were investigated using in vivo experimental models of inflammation and pain in mice, and also total phenolic content of the plant was determined. For the evaluation of the anti-inflammatory activity, carrageenan-induced paw edema and for the assessment of antinociceptive activity, p-benzoquinone-induced nociception tests in mice were employed. The crude ethanol extract of the plant was sequentially fractionated into five subextracts, namely n-hexane, CHCl3, EtOAc, n-BuOH and remaining water subextracts. Further studies were carried out on the bioactive n-BuOH subextract. Through bioassay-guided fractionation and isolation procedures from active fraction, ten flavonoids, isorhamnetin-3-O-rutinoside (1), quercetin-3-O-rutinoside (2), quercetin-3-O-metylether (3), tiliroside (4), isorhamnetin-3-glucuronide (5), isorhamnetin-3-O-glucoside (6), quercetin-3-O-galactoside (7), quercetin-3-O-rhamnoside (8), quercetin (9) and manghaslin (10), and two oleanane-type saponins, momordin II b (11) and momordin II c (12), and one amino acid derivative compound, N-acetyltryptophan (13) were isolated, and their structures were established on the basis of spectroscopic techniques. The anti-inflammatory and antinociceptive activities of 1, 4, 6, 7 and 12 were investigated firstly in this study, and 4 and 7 were found to have the most potent inhibitory activity in used models. The present study demonstrates the anti-inflammatory and antinociceptive activities in in vivo experimental models, chemical composition and total phenolic content of S. grandis for the first time.