An intercalation system consisting of layered PMA crystals as the host material and amino‐functionalized azobenzene derivatives as the guests is studied. The intercalation of difunctional guest molecules yields low conversions compared to the intercalation results using the corresponding monofunctional guests. Investigation of the cis–trans photoisomerization of the intercalated azo compounds reveals that the isomerization rate depends on the packing structure and the mobility of the azobenzene moieties in the host crystals. The monofunctional azobenzene moieties with a longer alkyl spacer undergo fast and reversible photoisomerization. XRD and UV results reveal the arrangement of the guest molecules present in the interlayer space of the host PMA crystals.