Eswatini, formerly known as Swaziland, is one of only 13 countries that officially recognise Taiwan over China, which claims the self-ruled island as its own territory.
Tsai arrived on Tuesday and held talks with King Mswati III, Africa's last absolute monarch.
They witnessed the signing of a memorandum of understanding on a women's entrepreneurship fund, and a memorandum of cooperation on the construction of a strategic oil reserve facility in Eswatini, Tsai's office said.
"I look forward to a successful execution of this project so that we will be able to establish a strategic oil reserve facility here to make the supply of energy more secure in the future," Tsai said, according to a video released by her office on Wednesday.
No further details were given about the memorandum.
Eswatini, which has struggled with fuel shortages in recent years, was left as Taipei's last African ally in 2018 when Burkina Faso switched diplomatic recognition to Beijing.
Two years ago, Mswati III praised Tsai for sending an anti-viral drug that helped him recover from Covid-19 at a time when the country of 1.2 million people was still waiting for its first vaccines against the disease.
This is Tsai's second trip to the kingdom, during which she will attend celebrations marking its independence day, the king's 55th birthday, and the 55th anniversary of Taiwan-Eswatini diplomatic ties.
She expressed hope on Tuesday that the friendship between the two countries "will continue and deepen".
Tsai came to power in 2016 and refuses to accept that Taiwan is a part of China.
Since then, Beijing has poached nine of Taipei's diplomatic allies and ramped up military pressure.
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