A multi-material active structure is a mechanical system made of passive and active materials with the ability to alter its configuration, form, or properties in response to changes in the environment. Active structures have been investigated to design lightweight structures and structures with the ability to “smartly” alter their shapes and/or internal forces. Recently, the potential of active structures to reduce environmental impact, i.e., reduce energy consumption and greenhouse gas (GHG) emissions, has been investigated. It has been verified that, compared to passive structures, active structures can not only use less material but also consume less energy and cause less GHG emissions during their service life, and thus have a significant potential to be applied as environment-friendly mechanical structures. This study aims to develop a general topology optimization (TO) approach to design novel multi-material active structural systems to reduce environmental impact. The approach is based on the density-based TO scheme. Passive and active materials are considered in the TO process and are required to be optimally distributed according to the optimization objective and constraints. The energy consumption or GHG emissions caused by the structure during its service life are treated as the objective function to be minimized under multiple displacement requirements. Typical examples are carried out to verify the developed approach. Results show that the topology optimized active structures may not only achieve significant weight savings but also less energy consumption and GHG emissions compared to equivalent topology optimized passive structures, which indicates that the developed approach has the potential to be applied to design novel structural systems with lighter weight, larger span, and with less environmental impact compared to conventional passive structural systems.