CSS Grid is a powerful tool for creating complex and responsive grid-based layouts. To ensure maintainability and flexibility, it's essential to follow best practices such as using flexible units for grid track sizes, choosing appropriate grid structures, carefully selecting positioning methods, nesting grids when needed, adding multiple grids on one page, combining CSS Grid with Flexbox, and testing responsiveness. By incorporating these practices, you can create visually stunning modern web layouts that adapt seamlessly to different screen sizes and devices.