The present disclosure belongs to the field of biopharmaceuticals, and in particular, relates to a multi-domain active protein for treating metabolic diseases. The multi-domain active protein has a structural formula as shown in Formula I: A-La-F-Lb-B. The multi-domain active protein of the present disclosure has a long half-life and supports a once-a-week administration frequency. The GLP-1R agonist activity of the multi-domain active protein is increased up to over 200 times. The multi-domain active protein has good stability in vitro and in vivo, and shows low immunogenicity potential. As introduction of non-natural amino acids is not required and chemical synthesis and crosslinking steps are not involved, the multi-domain active protein can be prepared recombinantly. Therefore, the preparation process is greatly simplified.