This work evaluates in vitro interaction of food components with artemether__ampersandsignndash;lumefantrine (AL) in tablet. Pelletized food components (i.e., starch, albumin, sunflower oil and carbonated drink) with AL tablet were observed using Fourier transform infrared (FTIR) spectroscopy while spectra obtained were compared using essential FTIR (eFTIR) software. The influence (i.e., instantaneous change in pH (IPH) and acid buffering capacity (ABC)) of food components on Fasted State Simulated Gastric Fluid (FaSSGF) and Fed State Simulated Intestinal Fluid (FeSSIF) were assessed alongside dissolution kinetics of actives in AL tablets. Artemether and lumefantrine produced identical spectra features with reference infra red (IR) spectra. No change in spectra features of AL on carbohydrate, vitamin A and oil treatment but noted with albumin and the carbonated drinks. IPH values for albumin revealed statistical higher value (p __ampersandsignlt; 0.05) than other food components in FaSSGF. ABC for albumin treatment was statistically lower (p __ampersandsignlt; 0.05) than for other food components in FaSSGF. Artemether overall release was significantly reduced by starch, lactose and carbonated drink (p __ampersandsignlt; 0.05) while that of lumefantrine was significantly increased by sunflower oil (p __ampersandsignlt; 0.05). There was interaction between AL and albumin, or carbonated drinks which can be of importance in drug treatment outcome.