Anabasis articulata (Chenopodiaceae), commonly called Ajrem, is a medicinal plant of Algerian flora of arid and semiarid regions, extensively used in complementary medicine to treat diabetes, eczema, fever, and kidney diseases. The current investigation was intended to evaluate the anti-inflammatory potential of A. articulata ethanolic extract (EEAA) and its fractions that were separated using decreasing polarity solvents (hexane, chloroform, ethyl acetate, and butanol) to obtain an ethanolic extract (EEAA), a chloroform extract (ChFA), an ethyl acetate extract (EAFA), an n-butanol extract (nBFA), and an aqueous extract (AqFA). These fractions were analyzed using LC-MS-MS, whereas polyphenols, flavonoids, and tannins were evaluated using colorimetric methods. For the acute toxicity study, one oral dose of 2 and 5 g/kg was administered to mice. The in vitro anti-inflammatory properties were determined by using the egg albumin denaturation test, whereas the in vivo anti-inflammatory effect was assessed using carrageenan, croton oil, and xylene-induced edema tests. The anti-inflammatory properties of these natural compounds were assessed in silico via molecular docking simulations applying the cyclooxygenase COX2 inhibitory impact. Seven metabolites were identified: anthrone, beta-carotene, butylated hydroxyanisole, butylatedhydroxytoluene, gallic acid, myricetin, and rutin. ChFA contained the greatest quantity of polyphenols and flavonoids (497.98 +/- 0.377 mg GAE/g and 79.89 +/- 0.789 mg QE/g). While nBFA showed the highest amount of total tannins (162.89 +/- 2.103 mg TAE/g). The evaluation of the in vitro anti-inflammatory properties revealed that all fractions of A. articulata had a potent anti-inflammatory effect. No death, no toxicological symptoms, and no appreciable body weight changes between the treated and control groups were observed. Oral administration of EEAA (200 mg/kg) significantly reduced the edema induced by carrageenan, croton oil, and xylene. The molecular docking showed that beta carotene, myricetin, and rutin exhibited the most promising inhibition against COX2. Significant anti-inflammatory effects were demonstrated by A. articulata extract in vitro, in vivo, and in silico. The administration of A. ariculata ethanolic extract can be regarded as non-toxic. These findings are consistent with the plant's traditional applications, which include therapy of anti-inflammatory illnesses.