In this study, corn starch and ibuprofen are treated in Argon (Ar) plasma to enhance the wettability of the powders without using any additive or guest particle. The powder and pellets were exposed to the Ar plasma for different time intervals (5–20 min) at optimized pressure and voltage. While the morphological changes due to plasma exposure are captured by SEM, the AFM measurement shows the variations in surface roughness for both corn starch and ibuprofen powders. The XPS and surface energy results confirm that the surface groups change is dominating under initial exposure, but longer exposure creates more damaging effect than building the new active sites at the surface. The contact angle (CA) measurement shows that with increase in treatment time, the CA decrease from 48° to 33° for corn starch and 69° to 51° for ibuprofen. A comparison of experimentally obtained CA and that of theoretically calculated CA shows that there exists some difference. This may be attributed to the absence of surface group contribution in the Wenzel model. The present study shows that short exposure is sufficient enough to improve the wetting where the surface group plays a dominant role over surface roughness.