The protection and renewal of historical and cultural districts are receiving increasing attention. Nevertheless, many of them undergo huge gaps in vitality between day and night and existed researches lack consideration of vitality assessment in multiple time dimensions. As a response to this situation, based on multi-source data and new technologies, we proposed a digital analysis and design method for historical and cultural district from the perspective of spatiotemporal vitality. Key evaluation dimensions were extracted and analyzed by integrating classic theory of urban design and spatial vitality, which were then quantitatively analyzed and illustrated to discover areas with insufficient spatiotemporal vitality, thus allowing for targeted strategies and design. Moreover, utilizing the quantitative benefits provided by multi-source data, the continuation of area’s spatiotemporal vitality and the enhancement of its spatial richness can be quantitatively assessed. In short, this study contributes to an exploration of the relationship between the spatial vitality, functional characteristics and spatial perception of historical and cultural district under spatiotemporal dynamics. And it establishes a method for quantitatively evaluating design effectiveness, while conducting design intervention and effectiveness evaluation. Meanwhile, it makes a step forward for providing embedded support across multiple stages from status analysis to design and evaluation, so that provides method for the consistency of spatiotemporal vitality in historical and cultural districts.