Non-contrast computed tomography (CT) is commonly used for the evaluation of various pathologies including pulmonary infections or urolithiasis but, especially in low-dose protocols, image quality is reduced. To improve this, deep learning-based post-processing approaches are being developed. Therefore, we aimed to compare the objective and subjective image quality of different reconstruction techniques and a deep learning-based software on non-contrast chest and low-dose abdominal CTs. In this retrospective study, non-contrast chest CTs of patients suspected of COVID-19 pneumonia and low-dose abdominal CTs suspected of urolithiasis were analysed. All images were reconstructed using filtered back-projection (FBP) and were post-processed using an artificial intelligence (AI)-based commercial software (PixelShine (PS)). Additional iterative reconstruction (IR) was performed for abdominal CTs. Objective and subjective image quality were evaluated. AI-based post-processing led to an overall significant noise reduction independent of the protocol (chest or abdomen) while maintaining image information (max. difference in SNR 2.59 ± 2.9 and CNR 15.92 ± 8.9, p < 0.001). Post-processing of FBP-reconstructed abdominal images was even superior to IR alone (max. difference in SNR 0.76 ± 0.5, p ≤ 0.001). Subjective assessments verified these results, partly suggesting benefits, especially in soft-tissue imaging (p < 0.001). All in all, the deep learning-based denoising—which was non-inferior to IR—offers an opportunity for image quality improvement especially in institutions using older scanners without IR availability. Further studies are necessary to evaluate potential effects on dose reduction benefits.