Heat-resistant spores on a dry, heat- and water-sensitive food matrix are difficult to inactivate. Radioactive or X-ray exposure is allowed and accepted only for some selected commodities. Non-thermal atmospheric pressure plasma treatments could offer an efficient, fast, and chemical-free solution. The effectiveness of direct contact cold atmospheric plasma (CAP) generated by a dielectric barrier discharge (DBD) device and air as process gas was evaluated against spores of Bacillus spp., Geobacillus spp., and Penicillium spp. A maximum of 3 log10 cycles of inactivation was achieved for B. coagulans spores exposed for only 10 s at low surface energy of 0.18 W/cm2 determined directly at the electrodes. This corresponds to an initial decimal reduction time of D1 = 0.1 min. Spores of B. subtilis are the most resistant amongst the studied strains (D1 = 1.4 min). The determining parameter in the modeling of the inactivation curve is surface energy. Non-porous, native starch granules or shells from diatoms, a highly porous material, were also contaminated with spores and treated by DBD CAP. The inactivation level was significantly reduced by the presence of powders. Considering plasma diagnostics, it can be concluded that the spore shell is the primary and main target for a plasma-induced inactivation. The inactivation affect scales with surface energy and can be controlled directly via process time and/or discharge power.