Medicinal mushroom extracts (MMEs) exert immunomodulatory effects on innate immunity. The present study aimed to examine the effect of medicinal mushroom components onin vitroimmune cell responses to inflammatory stimuli by peripheral blood mononuclear cells (PBMCs) isolated from older adults, where immune function is altered. PBMCs were treated with extracts fromHericium coralloides(HC) andTrametes versicolor(TV) prior to stimulation with rhinovirus A1 (RVA1), influenza A/H1N1pdm09 (H1N1), lipopolysaccharide (LPS), or house dust mite (HDM) for 48 h. In the presence of virus, type I and II IFN significantly (p< 0.05) decreased following treatment with at least one concentration of all extracts compared to the untreated cell controls, along with significant increases in pro-inflammatory cytokines (IL-1β, IL-6, IL-8). In the presence of LPS, extracts from TV reduced IL-1β compared to untreated cells. In the presence of HDM, the concentration of IL-5 and/or IL-13 was significantly decreased with at least one dose of all extracts. MMEs exert differential effects on the release of inflammatory and antiviral mediatorsin vitro. Reduced type 2 cytokine responses to HDM may be beneficial in conditions where allergic inflammation is present, including asthma, allergic rhinitis, and eczema. Further research is needed to examine extractsin vivo.