Microalgae are considered the biological drug factories of the future. To benefit from these microfactories, the intracellular metabolite of algae should be extracted. One of the most economically competitive methods is the ultrasound technique. This study was concerned with ultrasound-assisted extractions of useful substances from microalgae by comparing direct and indirect irradiation methods with respect to the extraction rate and yields. It is most likely that the direct and indirect irradiations had different irradiation powers. The systems were exposed to ultrasound wave (1.7 MHz) for 240min. For each system, the changes of optical density, concentration and biovolume of Chlorella were estimated. In addition, the concentration of extracted chlorophylls (a, b and a+b), carotenoid and lipid were measured. The factors were studied after 30, 60, 120, 180 and 240 min of exposure to ultrasound irradiation. Both direct and indirect irradiation systems produced cavitation in the cell membrane, and they reduced the concentration and biovolume of the Chlorella cells. The amount of lipids and chlorophylls was greater in the direct irradiation as compared to the indirect one, and it caused more cell disruption. However, the extraction of the carotenoid was less effective because direct irradiation produced more transmitted power of ultrasound, resulting in degradation of carotenoid. The results and analysis presented in this research showed that selection of the best method of irradiation is an important step, and it depends on the biomaterials to be extracted.