Plasmodium infection results in clinical presentations that range from symptomatic to severe malaria, resulting in about 500,000 deaths annually worldwide. Artemisinin-based Combination Therapies (ACTs) has largely been responsible for the significant reduction in malaria-related mortality in tropical and sub-tropical regions. However, this progress is seriously threatened by the reduced clinical efficacy of artemisinins, which is characterized by delayed parasitic clearance and high rate of recrudescence. In order to evaluate the synergistic effect of probiotics and antimalarial drug, in the treatment of malaria, the combination of artemether-lumefantrine and arthrospira platenis was administered to malaria patients and the gut microbiota and malaria parasite burden assessed during seven days follow-up. Of 313 subjects aged 2 to 18 years screened for malaria parasites, 75 participants were eligible to participate in this study. These participants were randomized and assigned to 3 groups to receive either the combination of Artemether-Lumefantrine and Arthrospira platensis (AL + AP), n = 25), designated as malaria positive group1 or Artemether-Lumefantrine (AL, n = 25), labeled malaria positive group 2 or to receive no antimalarial drug for malaria negative participants (n = 25, group 3). Fecal samples were collected on day 0 pre-treatment from all study participants and days 3 and 7 post-treatment from malaria positive patients for culture analysis and identification of gut microbiota communities. There was a significant change in the number of bacteria communities among treatment groups on days 3 and 7 post-treatment. Results from fecal sample culture analysis showed that E. coli was relatively abundant on day 3 (9 × 104 CFU/ml) and day 7 (9 × 104 CFU/g) as compared to day 0 (7 × 104 CFU/ml), Klebsiella was relatively abundant on day 3 (6 × 104 CFU/g) and day 7 (6 × 104 CFU/g) as compared to day 0 (5 × 104 CFU/ml), Pseudomonas was relatively abundant on day 3 (5 × 104 CFU/g) as compared to day 0 (4 × 104 CFU/ml) and day 7 (4 × 104 CFU/ml), Enterococci faecalis was relatively abundant on day 0 (5 × 104 CFU/ml) as compared to day 3 (3 × 104 CFU/ml) and day 7 (4 × 104 CFU/ml). In all treatment groups, the results showed that administration of arthemether-lumefantrine and Arthrospira to malaria positive subjects had a significant change on gut bacteria community on day 3 and day 7 post-treatment. In addition, malaria infected patients administered clinically relevant doses of artemether-lumefantrine and Arthrospira platensis had a significantly lower average parasitaemia on day 1 and day 2 as compared to malaria infected patients administered artemether-lumefantrine only. Therefore, the combination of artemether-lumefantrine and Arthrospira platensis in the treatment of malaria modifies the gut bacteria community which intend modulates malaria severity rapidly than artemether-lumefantrine alone. Collectively, these results identify the treatment of malaria with artemether-lumefantrine and Arthrospira platensis as potential treatment to decrease parasite burden.