Bioactive peptides are known to have many health benefits beyond nutrition; yet the peptide profile of high protein ingredients has been largely overlooked when considering the effects of different processing techniques. Therefore, to investigate whether drying conditions could affect the peptide profile and bioactivity within a functional ingredient, we examined the effects of spray (SD) and freeze (FD) drying on rice natural peptide network (NPN), a characterised functional ingredient sourced from the Oryza sativa proteome, which has previously been shown to effectively modulate circulating cytokines and improve physical performance in humans. In the manufacturing process, rice NPN was either FD or SD. Employing a peptidomic approach, we investigated the physicochemical characteristics of peptides common and unique to FD and SD preparations. We observed similar peptide profiles regarding peptide count, amino acid distribution, weight, charge, and hydrophobicity in each sample. Additionally, to evaluate the effects of drying processes on functionality, using machine learning, we examined constituent peptides with predicted anti-inflammatory activity within both groups and identified that the majority of anti-inflammatory peptides were common to both. Of note, key bioactive peptides validated within rice NPN were recorded in both SD and FD samples. The present study provides an important insight into the overall stability of the peptide profile and the use of machine learning in assessing predicted retention of bioactive peptides contributing to functionality during different types of processing.