Monoclonal antibodies, particularly nanobodies, have emerged as key therapeutics. However, their development remains challenging, with animal immunization or patient-derived antibodies being the gold standard for generating therapeutic antibodies. To address this, a deep learning tool called AbNatiV has been developed to assess the nativeness of antibodies and nanobodies, predicting their likelihood of belonging to the distribution of immune-system-derived human antibodies or camelid nanobodies. AbNatiV provides an interpretable score and residue-level profile to guide antibody engineering. The tool also includes an automated humanization pipeline, which has been shown to retain binding and stability in humanized nanobodies at par or better than wild-type. Laboratory experiments on two nanobodies demonstrate that AbNatiV-humanized nanobodies maintain or improve binding and stability compared to conventional humanization methods. AbNatiV is available as downloadable software and a webserver, offering a valuable tool for computational antibody design and ranking of Fv sequences from diverse sources.Monoclonal antibodies, particularly nanobodies, have emerged as key therapeutics. However, their development remains challenging, with animal immunization or patient-derived antibodies being the gold standard for generating therapeutic antibodies. To address this, a deep learning tool called AbNatiV has been developed to assess the nativeness of antibodies and nanobodies, predicting their likelihood of belonging to the distribution of immune-system-derived human antibodies or camelid nanobodies. AbNatiV provides an interpretable score and residue-level profile to guide antibody engineering. The tool also includes an automated humanization pipeline, which has been shown to retain binding and stability in humanized nanobodies at par or better than wild-type. Laboratory experiments on two nanobodies demonstrate that AbNatiV-humanized nanobodies maintain or improve binding and stability compared to conventional humanization methods. AbNatiV is available as downloadable software and a webserver, offering a valuable tool for computational antibody design and ranking of Fv sequences from diverse sources.