The mechanism through which Hydrangea macrophylla are able to change color has been the focus of investigation for many studies. However, the molecular mechanism involved in the complexation of aluminum ions and anthocyanins to regulate the color change remains unclear. Here, the color-changing mechanism was investigated in Hydrangea macrophylla plants under aluminum stress using proteome and transcriptome sequencing methods. Catalase, peroxidase, superoxide dismutase, 3-O-delphinidin and Al³⁺ contents in sepal were significantly upregulated upon Al³⁺ treatment. Moreover, 1628 differentially expressed genes and 448 differentially expressed proteins were identified between the treated and untreated conditions. GO and KEGG enrichment analyses revealed that the differentially expressed genes and differentially expressed proteins were enriched in categories related to the cell wall, peroxidase activity, and peroxisome pathways. Importantly, eight genes involved in anthocyanin biosynthesis were significantly downregulated at the transcript and protein levels under aluminum stress. These results suggest that aluminum ions induce expression changes of related key genes, which regulate the hydrangea’s flower color. Overall, this study provides a valuable reference for the molecular mechanism relating to the color change and adaptation of Hydrangea macrophylla in response to aluminum stress.