Biodegradable polymers are increasingly employed at the heart of therapeutic devices. Particularly in the form of thin and elongated fibers, they offer an effective strategy for controlled release in a variety of biomedical configurations such as sutures, scaffolds, wound dressings, surgical or imaging probes, and smart textiles. So far however, the fabrication of fiber-based drug delivery systems has been unable to fulfill significant requirements of medicated fibers such as multifunctionality, adequate mechanical strength, drug loading capability, and complex release profiles of multiple substances. Here, a novel paradigm in the design and fabrication of microstructured biodegradable fibers with tailored mechanical properties and capable of predefined release patterns from multiple reservoirs is proposed. Different biodegradable polymers compatible with the scalable thermal drawing process are identified, and their release properties as thin films of various thicknesses in the fiber form are experimentally investigated and modeled. Multimaterial microstructured fibers with predictable complex release profiles of potentially different substances are then designed and fabricated. Moreover, the tunability of the mechanical properties via tailoring the drawing process parameters is demonstrated, as well as the ability to weave such fibers. This work establishes a novel platform for biodegradable microstructured fibers for applications in implants, sutures, wound dressing, or tissue scaffolds.