To study the subcellular architectures and functions in a homeostatic environment, biologists seek to observe the biological processes inside structurally intact tissue at the molecular scale. This requires that fluorescence imaging methods be adapted and optimized to achieve sufficiently high spatial resolution in three dimensions at depth in live samples. Three-dimensional structured illumination microscopy (3D-SIM) is a super-resolution technique compatible with live-cell imaging. It can double the resolution in all three dimensions with optical sectioning, providing eight-fold more information than conventional widefield microscopy and enhanced image contrast. However, the application of SIM has been limited to single cells due to the degradation in image quality caused by optical aberrations in thick tissues which can be especially severe when imaging deep into live organisms. SIM relies on an ideal and uniform point spread function of the microscope system, and the optical aberrations not only lead to noise, artifacts, loss of image contrast, and resolution degradation in SIM images but can also prevent the SIM reconstruction algorithm from finding a solution at all. Therefore, to successfully implement 3D-SIM in thick tissues, a precise correction of the optical aberrations is critical.In this thesis, we demonstrate the application of Adaptive Optics (AO) to 3D-SIM, achieving effective aberration correction and resolution of 150 nm laterally and 570 nm axially at a depth of 80 µm in C. elegans. We demonstrate three AO methods, including the widefield sensorless AO method, the confocal sensorless AO method, and the direct wavefront sensing method using a confocal spot as the ‘guide-star’ for a Shack-Hartmann Wavefront Sensor. Through imaging a variety of biological samples, from cells to C. elegans, we experimentally demonstrate that 3D-SIM images clearly reveal the object of interest in all three dimensions, and the application of AO yields a significant improvement in the image resolution and contrast. In addition, we explore extending the resolution of our approach through nonlinear SIM, using the fast photoswtichable fluorescent protein, rsEGFP2. We experimentally demonstrate the nonlinearity using the patterned depletion approach on live cells labelled with rsEGFP2, showing the potential for fast live cell imaging at ~80-nm resolution.