At-home tooth whitening solutions with good efficacy and biosafety are highly desirable to meet the ever-growing demand for aesthetic dentistry. As a promising alternative to the classic peroxide bleaching that may damage tooth enamel and gums, piezocatalysis has been recently proposed to realize non-destructive whitening by toothbrushing with piezoelectrical particles. However, traditional particles either pose potential threats to human health or exhibit low piezoresponse to weak mechanical stimuli in the toothbrushing. Here, biocompatible and biodegradable polylactide particles constructed from interlocking crystalline lamellae have been hierarchically designed as next-generation whitening materials with ultra-high piezocatalytic activity and biosafety. By simultaneously controlling the chain conformation within lamellae and the porosity of such unique lamellae network at the nano- and microscales, the particles possessing unprecedented piezoelectricity have been successfully prepared due to the markedly increased dipole alignment, mechanical deformability, and specific surface area. The piezoelectric output can reach as high as 18.8 V, nearly 50 times higher than that of common solid polylactide particles. Consequently, their piezocatalytic effect can be readily activated by a toothbrush to rapidly clean the teeth stained with black tea and coffee, without causing detectable enamel damage. Furthermore, these particles have no cytotoxicity. This work presents a paradigm for achieving high piezoelectric activity in polylactide, which enables its practical application in tooth whitening.