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Fourteen plants endogenous to Sudan were selected to evaluate their total phenolic content, antioxidant, antimalarial and cytotoxicity potential in the present work. Extracts were prepared by maceration of each plant material in chloroform: methanol (C: M; 1:1 v/v) mixture. The antioxidant activity was determined by measuring the radical scavenging effects against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric-reducing (FRAP) capacity. The antiplasmodial activity was determined using the NF54 strain of <i>Plasmodium falciparum</i>. Cytotoxicity was evaluated towards human colorectal carcinoma cell line (HCT-116), human hormone-sensitive and invasive breast cancer cell line (MCF-7), and human hormone-resistant breast cancer cell line (MDA-MB-231), in addition to endothelial normal EAhy-296 cell line. Results showed that the plants' total phenolic and flavonoid contents were variable. Of the 14 plant species, only <i>Burnatia enneandra</i> showed high <i>in vitro</i> antiplasmodial activity (IC₅₀ 5758 ɳg/mL). Some plants possessed considerable free radical scavenging ability and reducing power. <i>Coccinia grandis</i> fruit extract (IC₅₀ 13.23 ± 0.51 μg/mL) and <i>Geigeria alata</i> root extract (IC₅₀ 35.54 ± 0.27 μg/mL) displayed the highest DPPH and ABTS scavenging activity, respectively. <i>Striga hermonthica</i> whole plant extract exhibited the highest FRAP reducing power (107.15 ± 0.11 nmol Fe+2 eq./mg). At a 100 μg/mL concentration, <i>Dioscorea hirtiflora</i> bulb extract displayed the highest cytotoxicity (74.23 ± 03.72%), followed by <i>Mitragyna inermis</i> fruit extract (65.28 ± 04.60%) against HCT-116 cell line. <i>Aerva javanica</i> leaf extract showed toxicity to the MDA-MB-231 cell line (50.82 ± 07.46%) at 100 μg/mL. The current study results showed that endogenous medicinal plants might represent a rich source of natural antioxidant, antimalarial and antitumor agents.