Spray drying fruit juice powders poses challenges because sugars and organic acids with low molecular weight and a low glass transition temperature inherently cause stickiness. This study employed a hydrophobic polytetrafluoroethylene (PTFE) film to mimic the surface of the drying chamber wall. The Central Composite Design (CCD) using response surface methodology investigated the impact of power (X1, Watt) and the duration of oxygenated plasma treatment (X2, minutes) on substrate contact angle (°), reflecting surface hydrophobicity. To validate the approach, Morinda citrofolia (MC) juice, augmented with maltodextrins as drying agents, underwent spray drying on the improved PTFE-coated surface. The spray drying process for MC juice was performed at inlet air temperatures of 120, 140, and 160°C, along with Noni juice-to-maltodextrin solids ratios of 4.00, 1.00, and 0.25. The PTFE-coated borosilicate substrate, prepared at a radio frequency (RF) power of 90W for 15 minutes of treatment time, exhibited a porous and spongy microstructure, correlating with superior contact angle performance (171°) compared to untreated borosilicate glass. Optimization data indicated that the PTFE film attained an optimum contact angle of 146.0° with a specific combination of plasma RF operating power (X1 = 74 W) and treatment duration (X2 = 10.0 minutes). RAMAN spectroscopy indicated a structural analysis with an ID/IG ratio of 0.2, while Brunauer-Emmett-Teller (BET) surface area analysis suggested an average particle size of less than 100 nm for all coated films. The process significantly improved the powder’s hygroscopicity, resistance to caking, and moisture content of maltodextrin-MC juice. Therefore, the discovery of this modification, which applies oxygen plasma treatment to PTFE-coated substrates, effectively enhances surface hydrophobicity, contact angle, porosity, roughness, and ultimately improves the efficacy and recovery of the spray drying process.