Technologies for controlling microbial risks in a heat and humidity sensitive food powder are still limited. To preserve bioactive compounds while inactivating Bacillus subtilis spores in powdered Spirulina microalgae (Arthrospira platensis) with a non-thermal atmospheric plasma is the challenge presented in this paper. Artificially contaminated powder was treated with a custom-made surface micro-discharge cold atmospheric pressure plasma (SMD-CAPP) at the effective, specific surface energy of the plasma (Es) of 7–15 mW/cm2. The inactivation of spores in air plasma was faster than in nitrogen plasma. The final effect after 5 min exposure time of close to 2 log10 reduction could be achieved with both plasma types but at different Es. Matrix effects resulted in bi-phasic inactivation kinetics, while single-phasic kinetics were observed for exposure without powder matrix. Chlorophyll-a, carotenoid, and phycobilin concentrations were more reduced by an exposure of the powder to an air plasma, compared to nitrogen plasma. Unexpectedly, the total phenolic content (TPC) increased by a factor of up to 2 at a nitrogen plasma treatment, while a decreasing TPC was observed with increasing plasma (or discharge) energy in an air plasma. Similar effects were identified for the Trolox equivalent antioxidant capacity (TEAC). The liberation of phenolic compounds from biopolymers and the decrease of scavenging compounds by the plasma treatment are supposed being responsible for simultaneous but opposite reactions influencing TPC and TEAC values. Furthermore, the scavenging capacity might reduce the inactivation of spores as observed with the nitrogen versus the air plasma. The failure of a higher spore inactivation relates to structure effects of the powder and improvements are supposed to be reached by a powder fluidization. The application of nitrogen plasma is preferred to that of air plasma for the decontamination of Spirulina powders when the preservation of bioactive compounds is the paramount objective.