Epigenetic DNA and histone modifications alter chromatin conformation and regulate gene expression. A major DNA modification is methylation, which is catalyzed by DNA methyltransferase (Dnmt) and results in gene suppression. Compared to DNA, histones undergo a greater variety of modification types, one of which is the acetylation of lysine. While histone acetyltransferase (HAT) catalyzes acetylation and activates gene expression, histone deacetylase (HDAC) removes the modification and causes gene suppression. As precise regulation of these epigenetic marks on DNA and histones is critical for cellular functions, their dysregulation causes various diseases including cancer, metabolic syndromes, immune diseases, and psychiatric diseases. Therefore, elucidation of the epigenetic phenomena is important not only in the field of biology but also in medical and pharmaceutical sciences. Furthermore, this field is also attracting industrial interest, because small-molecule inhibitors modulate enzymatic activity for epigenetic modification and are used for cancer treatment. Under these circumstances, various methods for detecting epigenetic modifications have been developed. However, most methods require cell lysis, which is not suitable for real-time detection of enzymatic activity. Since fluorescent probes are attractive chemical tools to solve this issue, chemists made considerable efforts to create fluorescent probes for epigenetics. To date, we have particularly focused on HDAC activity and DNA methylation and have developed fluorescent probes for their detection. The first part of this review describes our recent efforts to develop fluorescent probes for detecting HDAC activity. Since the discovery of HDAC activity in the late 1960s, no fluorescent probe has been developed that can detect enzymatic reactions in a simple, one-step procedure despite its biological and medical importance. We designed fluorescent probes to overcome this limitation by devising two different types of fluorescence switching mechanisms, which are based on aggregation-induced emission (AIE) and intramolecular transesterification. Using these probes, we detected HDAC activity simply by mixing the probes and HDAC for the first time. In the second part, a hybrid approach using a protein-labeling system was employed to detect DNA methylation in living cells. So far, live-cell detection of DNA methylation was conducted by imaging the localization of Fluorescent Proteins (FPs) fused to a methylated DNA-binding domain. However, FP lacks a fluorescence switch and emits fluorescence without binding to methylated DNA. We created a hybrid probe that comprises a fluorogen and a protein and enhances fluorescence intensity upon binding to methylated DNA. To create the hybrid probe, we applied our protein labeling system using the PYP-tag that we previously developed. This method successfully visualized methylated DNA in living cells and verified its dynamics during cell division. Both of the above-mentioned fluorescent probes have great potential for use not only in HDAC and DNA methylation but also in other epigenetics-associated modifications. For example, the mechanism of the HDAC probes can be used to detect histone demethylation. The hybrid probe can be converted to a sensor for imaging acetylated or methylated histones. In this review, we mainly describe how we designed the probes using chemical principles and solved the current obstacles with the probe design and discuss the future prospects of these probes.