Sea buckthorn is a promising species that, under the conditions of Eastern Europe, has shown high productivity and is also a good and possible source of a wide range of bioactive compounds that have a positive effect on the human body, especially polyphenols and carotenoids. Due to the content of biologically active substances in sea buckthorn (Hippophae rhamnoides L.), the species is of growing interest to scientists, the food industry, the pharmaceutical industry, the cosmetics industry and consumers. The aim of this study is to investigate the productivity and the correlation between the chemical composition and the antibacterial effect of four cultivars of sea buckthorn (Clara, Dora, Cora, Mara), cultivated in the Republic of Moldova. Sea buckthorn fruits were harvested at the stage of full ripening. Berry samples were frozen at minus 25 °C, stored for 6 months and whole fruits of sea buckthorn were studied. All quantitative characteristics were calculated in terms of absolutely dry raw material (dry weight). The sea buckthorn cultivars tested were found to have a different carotenoid contents (1.79–48.92 mg/100 g), ascorbic acid contents (74.36–373.38 mg/100 g), organic acids (malic acid 5.8–13.4 mg/100 g, citric acid 0.08–0.321 mg/100 g, succinic acid 0.03–1.1 mg/100 g), total dry matter contents (16.71–24.54%), titratable acidities (2.15–8.76%) and pH values (2.73–3.00). The antimicrobial activity of sea buckthorn, evaluated by the diameter of the inhibition zone, constituted for Bacillus pumilus 3.70–15.91 mm/g⁻¹ for whole sea buckthorn fruits and 13.33–26.67 mm/g⁻¹ for sea buckthorn purees.