Oat bran (OB) may be regarded as food industry by-product, with a high perspective as a bioresource in the production of high-value polyphenolic substances. On this basis, the investigation presented herein aimed at (i) using 1- and 2-propanol organosolv treatment and studying the effect of an alkali (sodium hydroxide) catalyst on releasing bound polyphenols, (ii) establishing models of polyphenol recovery by employing severity and response surface methodology, and (iii) investigating the polyphenolic profile of the extracts produced. Yield in total polyphenols as a function of treatment severity was satisfactorily described by linear models, indicating that for both 1- and 2-propanol treatments, temperature and time could be used interchangeably to adjust severity. Furthermore, the 1-propanol process was found to be more efficient at lower severity compared to the 2-propanol process. The optimization using response surface methodology revealed that, under identical condition settings (t = 300 min, T = 90 °C), the 1-propanol treatment afforded a total polyphenol yield of 17.15 ± 0.51 mg ferulic acid equivalents per g−1 dry mass, whereas the 2-propanol treatment gave a yield of 14.78 ± 1.11 mg ferulic acid equivalents per g−1 dry mass. Liquid chromatography–tandem mass spectrometry analyses showed that the extract produced from the 1-propanol treatment was significantly more enriched in ferulic acid and p-coumaric acid compared to the extract generated with the 2-propanol treatment. Moreover, the antioxidant activity of the extracts was in concurrence with the polyphenolic composition. Based on the evidence, the alkali-catalyzed, 1-propanol organosolv treatment of OB is proposed as a sustainable and efficient methodology to recover multipurpose natural antioxidants.