The Matheniko Wildlife Reserve is a conservation area in the Karamoja subregion of northeastern Uganda.

Matheniko is a part of the corridor of protected areas in Karamoja that stretches from Kidepo National Park down through Bokora and Pian Upe Wildlife Reserves.

Matheniko falls into the Somalia-Masai ecoregion of semi-desert grassland and shrubland.

Average annual rainfall in the Reserve is 670 millimetres (26 in), with peaks in April–May and in November.

[1] The Uganda Wildlife Authority is actively working to develop Matheniko's tourism infrastructure.