Abstract Acmella caulirhiza is a plant that belongs to the Asteraceae family used in traditional medicine to treat tonsillitis diseases, urinary tract infections, diaper rash, and oral diseases by different communities in Ethiopia. The purpose of this project was to study effect of different solvents in maceration and soxhlet methods, preliminary phytochemical screening, analysis of Total Phenol Content (TPC), and Total Flavonoid content (TFC). The study also aimed at analysis of fatty acid composition using Gas Chromatography Mass Spectrometry (GC-MS) from Acmella caulirihiza. To achieve this, different extracts from the Acmella caulirhiza plant were made using maceration method and Soxhlet apparatus. The extraction solvents used were methanol, ethanol, acetone, and petroleum ether. Extraction yield, phytochemical screening, total phenol concentration, and flavonoid concentration were evaluated to compare the efficiency of different extraction solvents. Extraction by maceration showed maximum yield in methanol 8 %; while the highest yield obtained with methanol was 13.2 % using Soxhlet method. Each extract was screened for phytochemicals such as flavonoids, phenols, tannins, coumarins, steroids, and terpenoids. The results shows that using methanol as an extraction solvent works best for the extraction of various active phytochemicals with total phenol content of 22.10 ± 2.05 mg gallic acid equivalent/g of extract, total flavonoid content of 9.71 ± 1.45 mg of quercetin equivalent/g of extract, which is significantly higher than petroleum ether which yielded in the minimum extraction with total phenol content of 15.74 ± 1.95 mg gallic acid equivalent/g of extract, total flavonoid content of 5.98 ± 0.90 mg of quercetin equivalent/ g of extract. The results showed that the fatty acid constituents in the GC-MS analysis, 10 fatty acid constituents were identified in the petroleum ether extract. The most abundant fatty acid was hexadecenoic acid (38.5%), followed by Linoleic acid (34.21%), (z)-9-octadecenoic acid (12.09%), Methyl stearate (6.54%), 12-methyltridecanoic acid (2.23%), (E)-9-Octadecenoic acid (1.46%), Pentacosanoic acid (1.4%). 6,9,12,15-Docanoic acid (0.94%) and 15-methylhexadecenoic acid (0.82%) are fatty acids were minor in concentrations. Our results clearly demonstrates that methanol is the best extraction solvent for the extraction of various phytochemicals extraction potential and Acmella caulirihiza plant may be considered as a good source of omega-6 fatty acid (linoleic acid), omega-7 fatty acid 6,9,12,15- docosaetraenoic acid (stearidonic acid) acid and omega-9 (z)-9-octadecenoic acid (oleic acid) and (E)-9-octadecenoic acid (elaidic acid) may be used for decaling heart disease, inflammation, and increasing immunity and also, hexadecenoic acid (palmitic acid) and methyl stearate (stearic acid) fatty acids used in the manufacture of soaps, cosmetics, lubricants and softening. It is therefore recommended that further work be undertaken to isolate the bioactive compound, determine the chemical identity of the active ingredient(s), and explore their potential for clinical, pharmacological or chemical/ industrial application