The effect of cold plasma (CP) on phenolic compound (PC) and biogenic amine (BA) contents of red wine was investigated for the first time. The influence of CP was compared with the effects of a wine preservation using potassium metabisulfite and a combined method. The PC profile was determined by UPLC-PDA-MS/MS while BAs using DLLME-GC-MS. Chemometric analysis also was used. The content of PCs was 3.1% higher in the sample preserved by CP treatment (5 min, helium/nitrogen) compared to a sample preserved by the addition of potassium metabisulfite (100 mg/L). On a positive note, CP treatment reduced the concentration of BAs in the wine samples. The lowest BA contents were recorded after 10 min of cold plasma (helium/oxygen) treatment with the addition of potassium metabisulfite (1120.85 μg/L). The results may promote interest in CP as a potential alternative method for the preservation of wine and other alcoholic beverages.