Objective: To investigate the antiplasmodial, antimicrobial, radical scavenging effects and to identifiy the phenolic constituents of Atriplex lindleyi (A. lindleyi). Methods: A. lindleyi extracts and some isolated compounds were tested in vitro against the chloroquine-resistant strains of Plasmodium falciparum. The radical scavenging activity was quantified by using 2,2-diphenyl-2-picrylhydrazyl nitrogen-centered free radical. The IC50 of each extract was compared with references. The in vitro anti-infectious activity of extracts was evaluated against representative Gram-positive and Gram-negative bacterial strains [Staphylococcus aureus CIP 4.83, Enterococcus hirae CIP 5855, Pseudomonas aeruginosa (P. aeruginosa) CIP 82118, Escherichia coli CIP 53126], and fungal species [(Candida albicans (C. albicans) IP 48.72, Aspergillus niger IP 1431.83]. Ethanol extract was investigated for chemical composition through column and high performance liquid chromatography. The isolated compounds were identified by mass spectrometry and nuclear magnetic resonance. Results: Quercetin-7-O-arabinopyranoside-3-O-neohesperidosides (1), quercetin-3- O-arabinopyranosyl(1→6)glucopyranoside (2), quercetin-3-O-glucopyranoside-7-Orhamnopyranoside (3), quercetin-3-O-glucopyranoside-7-O-arabinoside (4), schaftoside (5), quercetin-7-O-glucopyranoside (6) were isolated for the first time from the ethanol extract of A. lindleyi aerial parts in addition to isorhamnetin-3-O-β-glucopyranoside (7) and quercetin (8). The extracts exhibited moderate antiplasmodial activity with IC50≈ ranging from 10–50 μg/mL. Quercetin was the most potent compound with IC50 of 9 µg/mL. P. aeruginosa and C. albicans were the most susceptible organisms. Conclusions: The study implies that A. lindelyi can contribute to the fight against malaria, and be useful as prophylactic against C. albicans and P. aeruginosa.