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ABSTRACT Introduction Many chronic diseases have evolved and to circumvent the limitations of using conventional drug therapies, smart cell encapsulating delivery systems have been explored to customize the treatment with alignment to disease longevity. Cell therapeutics has advanced in tandem with improvements in biomaterials that can suitably deliver therapeutic cells to achieve targeted therapy. Among the promising biomacromolecules for cell delivery are those that share bio-relevant architecture with the extracellular matrix and display extraordinary compatibility in the presence of therapeutic cells. Interestingly, many biomacromolecules that fulfil these tenets occur naturally and can form hydrogels. Areas covered This review provides a concise incursion into the paradigm shift to cell therapeutics using biomacromolecules. Advances in the design and use of biomacromolecules to assemble smart therapeutic cell carriers is discussed in light of their pivotal role in enhancing cell encapsulation and delivery. In addition, the principles that govern the application of cell therapeutics in diabetes, neuronal disorders, cancers and cardiovascular disease are outlined. Expert opinion Cell therapeutics promises to revolutionize the treatment of various secretory cell dysfunctions. Current and future advances in designing functional biomacromolecules will be critical to ensure that optimal delivery of therapeutic cells is achieved with desired biosafety and potency.