Organic solid pharmaceutical powders are used for the preparation of various drug dosage forms. Primary particles in powder form undergo several processing steps first in pharmaceutical formulations followed by pharmaceutical manufacturing to final dosage form of a drug. These unit operations involve both handling of powders in aqueous or solvent solutions and drying. There will be a probable rise for a demand for the different unit operations in the requirements of protecting the active pharmaceutical ingredient or challenges in powder handling. Besides pharmaceutical manufacturing, there are many biological interfaces where control of surface characteristics of pharmaceutical powders can improve the therapeutic response and bioavailability. In this work, we have modified acetaminophen particles with atomic layer deposition (ALD) by conformal nanometer scale coatings in a one-step coating process. According to the results, ALD comprising common chemistries for Al2O3, TiO2 and ZnO is shown to be a promising coating method for solid pharmaceutical powders. Acetaminophen does not undergo degradation during the ALD coating and maintains its stable polymorphic structure. The nanometer scale ALD coating can sustain the drug release. ALD oxide coated acetaminophen particles show different cytocompatibility assessed in in vitro intestinal Caco-2 cells.