This study aimed to evaluate the impacts of cold plasma processing time of 30 s, 180 s, and 300 s (CSM30, CSM180, and CSM300) on the microbial inactivation, physicochemical characteristics, and protein structure of raw sheep milk. Pasteurized sheep milk was used as the positive control. The microbial inactivation rate of CSM300 sample was similar to the pasteurized sample, and the former had a significantly smaller casein micelle size and polydispersity index (P < 0.05). The pH, and a* value decreased from 6.79 to 6.65, and −1.74 to −1.98, respectively (P < 0.05) with increasing processing time. Also, the moisture content of the freeze-dried milk decreased from 43.4 g/kg to 28.9 g/kg. The Fourier-transform infrared spectra indicated that the CSM180 and CSM300 samples had higher proportions of β-turn structures and a diminished-random coil conformation, the latter could induce an appropriate conformational transformation from α-helix to β-sheet. Scanning electron microscopy images confirmed that the CSM300 sample promoted a more uniform microstructure and a better dispersion state of proteins. These results might provide practical information regarding cold plasma–treated sheep milk, which can be considered as a potential alternative to conventional pasteurization.