<p>Peptide-based drugs often fail in clinical trials due to their toxicity or hemolytic activity against red blood cells (RBCs). Existing methods predict hemolytic peptides but not the concentration (HC₅₀) required to lyse 50% of RBCs. This study develops classification and regression models to identify and quantify hemolytic activity. These models train on 1926 peptides with experimentally determined HC₅₀ against mammalian RBCs. Analysis indicates that hydrophobic and positively charged residues were associated with higher hemolytic activity. Among classification models, including machine learning (ML), quantum ML, and protein language models, a hybrid model combining random forest (RF) and a motif-based approach achieves the highest area under the receiver operating characteristic curve (AUROC) of 0.921. Regression models achieve a Pearson correlation coefficient (R) of 0.739 and a coefficient of determination (R²) of 0.543. These models outperform existing methods and are implemented in HemoPI2, a web-based platform and standalone software for designing peptides with desired HC₅₀ values (<a href="http://webs.iiitd.edu.in/raghava/hemopi2/">http://webs.iiitd.edu.in/raghava/hemopi2/</a>).</p>