<p>Solute segregation at grain boundaries (GBs) significantly influences the mechanical properties and stability of nanocrystalline aluminum (Al) alloys. However, the behavior of solute segregation and the underlying mechanisms affecting Al GB strength require further investigation. In this study, 52 solute elements from the periodic table were selected, and the segregation behavior and strengthening effect were analyzed by calculating segregation energies and enhancing energy using first-principles methods. The results reveal that segregation behavior, such as the segregation preference, is primarily influenced by atomic radius and electronic interactions. The calculated GB energy indicates that most solutes enhance GB stability. Furthermore, the strengthening energy results show that most elements from the s- and p-blocks weaken GB strength, while elements from the d-block generally strengthen it except for the V, Mo, and W, which increase the GB strength with positive segregation energy. The strengthening energy and segregation energy of the elements in the d- and p-block exhibit a concave curve and a decreasing distribution with the group number, respectively. The structural and charge density analysis exhibits that the weakening effect of Li and Si can be ascribed to the charge depletion in the core of GB, while the strengthening effect of Mn and Ce is the result of charge accumulation and segregation-induced structural variation. This study provides meaningful insights for designing high-strength nanocrystalline Al alloys.</p>