Mesembryanthemum edule (Aizoaceae) is an edible halophyte widely used as a traditional remedy against fungal and bacterial infections. This study investigates phenolic contents and biological activities of aqueous methanolic fractions (methanol/acidified water, v/v: 20/80, 40/60 and 60/40) of M. edule leaves, stems and roots. The most phenol-rich fractions were leaf 20%, stem 60%, and root 40% (from 671 to 989 mg GAE g−1 DR). The highest ferric reducing power was found in leaf 40% and stem 40% (86 and 94 μg ml−1, respectively) whereas the highest total antioxidant activity was noted in root 40% (395 mg GAE g−1 DR). Concerning the antimicrobial activity, organ extracts were assayed for their activity against food borne bacteria and fungi. The inhibitory percentages ranged from 0 to 94%. Stems showed the strongest antibacterial activity (inhibition of the growth in 6 of the 7 strains tested) especially against Micrococcus luteus (82%) followed by leaves and roots. Regarding fraction polarity, 60% and 20% aqueous methanolic fractions were the most and the less active fractions, respectively. All the organ fractions showed a high antifungal activity, notably against Kloeckera apiculata (85% for leaf 40%) and Candida albicans (77% for stem 40%). Even more, leaf, stem and root fractions were very potent in inhibiting growth of filamentous fungi, with inhibition percentages varying between 23% and 99%. Overall, the fractionation process enabled a better assessment of M. edule antioxidant and antimicrobial activities, which were attributed to various metabolites with different polarities. Our findings also indicate that M. edule organs could be used as a potent source of natural antioxidants and antibiotics.