Notwithstanding its level of socio-economic development, health failure is a threat to any country. Globally, the Covid-19 pandemic is believed to be the greatest threat to the existentiality of humanity since the end of World War II. The level of global interconnectivity also made it the most destructive to human existence. The accelerating growth of the pandemic in South Africa has devastated effects on its economy and cuttingly intensified prior socio-economic challenges and inadvertently, presented South Africa with an unseen and formidable enemy that does not know the differences between South African Black, Coloured, Indian or White. The study used a qualitative research approach, underpinned by the rationality for South Africa, to embrace innovative diplomacy as a means to an end for its health safety and security amidst the covid-19 pandemic. The paper argued that South Africa must innovatively engage the acceptable global mechanisms and other health security measures with focus on its commitment to the goals of its national interests, while strengthening the efficiency of its health initiatives through better-quality governance where both local and international investors are allowed to participate actively in state socio-economic activities that respond to the safety and health security of the emotionalized publics. Thus, in a globalised system of innovation, South Africa needs to see the innovation environment as a steady pipeline of its domestic ability to control the negative effect of Covid-19 on its national health security. The paper concludes that South Africa must begin to invest, modify, and localise the biotechnology industry, and thus serving as a source of employment for the teaming unemployed South Africans.