Bugisu sub-region is a region in Eastern Uganda that consists of the following districts:
- Bududa District
- Bulambuli District
- Manafwa District
- Mbale District
- Namisindwa District
- Sironko District
The sub-region is home mainly to the Gisu people, also called Bagisu, (singular is Mugisu). The Bagisu speak Lugisu, a dialect of Lumasaba, a Bantu language. Lugisu is very similar to the Bukusu language spoken of the Bukusu people of Kenya.
According to the 2002 national census, the Bugisu sub-region was home to an estimated 1 million people at that time.