A mouse with multi-configurable buttons is provided. The mouse with multi-configurable buttons comprises a housing, a cylinder module and a signal processing device. The housing has an opening, and the cylinder module is received in the housing and partially exposed through the opening. The cylinder module at least comprises a first click portion and the second click portion, and the signal processing device at least comprises a first switch and a second switch. When the first click portion is exposed through the opening, the first click portion is used for activating the first switch. In contrast, when the second portion is exposed through the opening, the second click portion is used for activating the first and the second switch. Therefore, the mouse with multi-configurable buttons provides at least two configuration status via rotating the rotating cylinder to satisfy different user demands.