In biological research and biomedical imaging, detailed visualization of cellular structures is essen- tial for advancing scientific discoveries. Traditional fluorescence microscopy, limited by the diffraction barrier, is inadequate for observing intricate cellular processes, such as mitochondrial dynamics and pro- tein synthesis. This limitation has led to the development of super-resolution microscopy techniques, which allow for visualization beyond the diffraction limit. This dissertation presents two advanced super- resolution imaging methods: Self-Interference Digital Holography-based 3D Single Molecule Localization Microscopy (SIDH-based 3D-SMLM) and 2D Non-linear Pattern Depletion Structured Illumination Microscopy (2D PD-NSIM).The SIDH-based 3D-SMLM combines digital holography with single molecule localization to achieve nanometer-scale resolution over a large axial imaging range without mechanical refocusing. This method overcomes the axial range limitations of traditional 3D-SMLM using Point Spread Function (PSF) en- gineering. A computational aberration correction approach is developed to further improve SIDH’s performance. Numerical simulations show that the optimized SIDH system can achieve lateral local- ization precision between 5 nm and 58 nm and axial precision between 13 nm and 80 nm, even at low signal-to-noise ratios (SNR). Experimental results demonstrate that the optimized SIDH system can successfully reconstruct a 100 nm microsphere with a low photon budget (∼ 4, 200 photons) over a 10 μm axial range. Additionally, with light sheet illumination, as few as ∼ 2, 120photons can be detected in a hologram. Furthermore, a fast guide-star-free computational aberration correction method is presented, demonstrating an improvement in both the Strehl ratio (up to ∼ 0.98) and SIDH localization precision (restored to near the ideal case). The second method, 2D PD-NSIM, utilizes structured illumination patterns and reversibly switchable fluorescent proteins to access higher frequency information from the sample. By introducing non-linear effects into the emission light, this method surpasses the traditional 2-fold resolution improvement of linear SIM, making it particularly advantageous for real-time super resolution live-cell imaging. This dissertation details the principles and implementation of 2D PD-NSIM and demonstrates its capability to achieve sub-80 nm resolution by imaging live biological samples. This dissertation provides significant advancements in super-resolution microscopy, offering new methodologies for high-resolution imaging of biological samples. Chapter 1 introduces the principles of fluorescence microscopy, optical imaging systems, and an overview of super-resolution techniques. Chap- ter 2 discusses SIDH-based 3D-SMLM, including the theoretical foundation, experimental validation, and aberration correction methods. Chapter 3 explains the principles of 2D PD-NSIM and details its reconstruction techniques along with experimental results from other studies. Chapter 4 focuses on the optimization of the SIDH system for single-molecule localization, while Chapter 5 presents a computa- tional aberration correction method for SIDH. Chapter 6 presents the experimental setup and results of 2D PD-NSIM using rsEGFP2, discussing synchronization, timing, and potential future developments. Finally, Chapter 7 concludes the dissertation by summarizing the main findings.