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The unicellular green microalga <i>Dunaliella</i> is a potential source of a wide range of nutritionally important compounds applicable to the food industry. The aim of this study was to assess the effect of <i>Dunaliella salina</i> dried biomass on the growth and adherence of 10 strains of <i>Lactobacillus</i>, <i>Lacticaseibacillus,</i> and <i>Bifidobacterium</i>. The immunomodulatory, antioxidant, and cytotoxic effects of <i>D. salina</i> on human peripheral mononuclear cells and simulated intestinal epithelial cell lines Caco-2 and HT-29 were evaluated. Furthermore, the hypocholesterolemic effects of the microalgae on lipid metabolism in rats fed a high-fat diet were analyzed. The addition of <i>D. salina</i> biomass had a positive effect on the growth of nine out of 10 probiotics and promoted the adherence of three bifidobacteria strains to human cell lines. The antioxidant and immunomodulatory properties of <i>D. salina</i> were concentration-dependent. The inflammatory cytokines (TNF-α and IL-6) were significantly increased following <i>Dunaliella</i> stimulation at the lowest concentration (0.5% <i>w/v</i>). Eight week supplementation of <i>D. salina</i> to the diet of hypercholesteromic rats significantly decreased the serum concentrations of LDL-C, VLDL, IDL-B, and IDL-C. <i>D. salina</i> is not cytotoxic in intestinal cell models; it promotes adherence of selected bifidobacteria, it affords immunomodulatory and antioxidant effects, and its addition to diets may help decrease atherosclerosis risk factors.