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The probiotic Bifidus BB536 (BB536), which contains <i>Bifidobacterium longum</i>, has been shown to have enhanced probiotic effects when given together with a standardized extract of cultured <i>Lentinula edodes</i> mycelia (AHCC^&#174;, Amino Up Co. Ltd., Sapporo, Japan). BB536 and AHCC^&#174; may modulate T cell and dendritic cell (DC) phenotypes, and cytokine profiles to favour anti-inflammatory responses following antibiotic ingestion. We tested the hypothesis that orally administered BB536 and/or AHCC^&#174;, results in modulation of immune effector cells with polarisation towards anti-inflammatory responses following antibiotic usage. Forty healthy male volunteers divided into 4 equal groups were randomised to receive either placebo, BB536, AHCC^&#174; or a combination for 12 days in a double-blind manner. After 7 days volunteers also received 250 mg azithromycin for 5 days. Cytokine profiles from purified CD3+ T cells stimulated with PDB-ionomycin were assessed. CD4+ CD25+ forkhead box P3 (Foxp3) expression and peripheral blood DC subsets were assessed prior to treatment and subsequently at 7 and 13 days. There was no difference in cytokine secretion from stimulated CD3+ T cells between treatment groups. Compared with baseline, Foxp3 expression (0.45 &#177; 0.1 vs. 1.3 &#177; 0.4; <i>p</i> = 0.002) and interferon-gamma/interleukin-4 (IFN-&#947;/IL-4) ratios were increased post-treatment in volunteers receiving BB536 (<i>p</i> = 0.031), although differences between groups were not significant. For volunteers receiving combination BB536 and AHCC^&#174;, there was an increase in myeloid dendritic cells (mDC) compared with plasmacytoid DC (pDC) counts (80% vs. 61%; <i>p</i> = 0.006) at post treatment time points. mDC2 phenotypes were more prevalent, compared with baseline, following combination treatment (0.16% vs. 0.05%; <i>p</i> = 0.002). Oral intake of AHCC^&#174; and BB536 may modulate T regulatory and DC phenotypes to favour anti-inflammatory responses following antibiotic usage.