Aims To screen the newly recorded alga Grateloupia doryphora in the Egyptian Mediterranean Sea for antimicrobial activity. Methods and ResultsConclusionsAlgal samples were collected from the Eastern Harbor, Alexandria, Egypt during summer (2016 and 2017). The dry and fresh methanolic, ethanolic and ethyl acetate algal extracts were tested against Bacillus subtilis, Enterococcus faecalis and Staphylococcus aureus as Gram-positive bacteria, Escherichia coli, Pseudomonas aeruginosa as Gram-negative bacteria and one yeast strain Candida albicans. A three-way analysis of variance showed significant differences based on the algal form, type of solvents and microbial species. The fresh methanolic and ethyl acetate extracts had equal effects on the tested pathogens with means of 1444 and 1516 respectively. However, the fresh algal extract was more effective on all the tested organisms than the dried material, except for ethyl acetate and ethanol extract on Bacillus subtilis (31 and 23mm) respectively. In fact, P. aeruginosa was the most susceptible organism to the fresh algal extract, with much higher inhibition zones (30, 27 and 28mm) for mehanolic, ethyl acetate and ethanolic extracts, respectively, compared with the dried ones. Furthermore, C. albicans was sensitive to the fresh algal extracts only. Compared with the commercial antibiotics piperacillin, rifampicin, cephalexin, metronidazole and fusidic acid tested against the same microbes, the results showed in general lower or comparable inhibition zones than algal extracts. The GC-MS fresh methanolic and ethyl acetate algal extracts revealed the presence of many potent compounds, with palmitic acid and 2-tetradecyloxirane as the common constituents in both extracts. The commercial palmitic acid was tested against the same microbes with successful elimination of all pathogens. Grateloupia doryphora showed broad spectrum of antimicrobial activity against the tested microbial species in this study. Significance and Impact of the StudyThe alga can be useful in industry of pharmaceutical products. On the other hand, its usage in this domain can be a suitable solution to its introduction in our coasts.